Escin ameliorates CUMS-induced depressive-like behavior via BDNF/TrkB/CREB and TLR4/MyD88/NF-κB signaling pathways in rats.

Major depressive disorder (MDD) is a prevalent psychiatric disorder associated with brain inflammation and neuronal damage. Derived from the Aesculus chinensis Bunge fruit, escin has shown anti-inflammatory and neuroprotective effects. However, its potential as a treatment for MDD is unclear. This study investigates the antidepressant properties of escin using in vivo experimentation. The chronic unpredictable mild stress (CUMS) model was used to analyze the potential antidepressant effects and underlying mechanisms of escin. Wistar rats were exposed to CUMS for 35 consecutive days to induce MDD. The rats were then given either escin (1, 3, and 10 mg/kg) or fluoxetine (2 mg/kg) on a daily basis. Notably, escin significantly alleviated the depressive behaviors induced by CUMS, as evaluated through a series of behavioral assessments. Moreover, escin administration reduced TNF-α, IL-1ß, and IL-6 levels in the hippocampus. It also decreased serum adrenal cortical hormone (ACTH) and corticosterone (CORT) levels while increasing 5-HT and Brain-derived neurotrophic factor (BDNF) levels in the CUMS rats, as measured by the enzyme-linked immunosorbent assay (ELISA). Pathological changes in the hippocampal regions were identified through Nissl staining, and Western blotting was used to quantify the protein levels of BDNF, TrkB, CREB, TLR4, MyD88, and NF-κB. Escin mitigated neuronal injury, elevated TrkB, BDNF, and CREB, and reduced TLR4, MyD88, and NF-κB protein levels in CUMS rats. The data from this study suggest that escin holds the potential for alleviating depression-like symptoms induced by CUMS. This effect may be mediated through the modulation of two signaling pathways, BDNF/TrkB/CREB and TLR4/MyD88/NF-κB.

Recent innovations in 3D solar evaporators and their functionalities.

Interfacial solar evaporation (ISE) has emerged as a promising technology to alleviate global water scarcity via energy-efficient purification of both wastewater and seawater. While ISE was originally identified and developed during studies of simple double-layered two-dimensional (2D) evaporators, observed limitations in evaporation rate and functionality soon led to the development of three-dimensional (3D) evaporators, which is now recognized as one of the most pivotal milestones in the research field. 3D evaporators significantly enhance the evaporation rates beyond the theoretical limits of 2D evaporators. Furthermore, 3D evaporators could have multifaceted functionalities originating from various functional evaporation surfaces and 3D structures. This review summarizes recent advances in 3D evaporators, focusing on rational design, fabrication and energy nexus of 3D evaporators, and the derivative functions for improving solar evaporation performance and exploring novel applications. Future research prospects are also proposed based on the in-depth understanding of the fundamental aspects of 3D evaporators and the requirements for practical applications.

3D­printed template­guided iodine­125 seed implantation to treat complete occlusion of the superior vena cava in pulmonary sarcomatoid carcinoma: A case report.

Pulmonary sarcomatoid carcinoma (PSC), which is a type of non-small-cell lung carcinoma (NSCLC), is characterized by a high degree of malignancy, poor differentiation and a high incidence of pulmonary malignancy. In addition, PSC has a stronger invasive ability than other types of NSCLC and is not sensitive to radiation or chemotherapy. Furthermore, 90% of PSC cases exhibit vascular invasion; therefore, there is a risk of multiple metastases to the lung, bone, adrenal glands and brain, and consequently a poor prognosis, in the early stage. Targeted therapy and immunotherapy currently offer a new treatment direction; however, there have not been any significant advances in localized treatment in recent years. Thus, there is an urgent need for new localized treatment strategies. The present study describes the case of a 65-year-old man with recurrence of PSC after multi-line treatment with chemotherapy, radiotherapy, gamma knife and argon-helium knife treatment. In addition, the patient developed superior vena cava syndrome, and exhibited severe compression of the superior vena cava, chest discomfort, dyspnea and severe facial edema after chemotherapy, local gamma knife therapy (35 Gy, delivered through 14 2.5-Gy doses), argon-helium knife therapy and radiation therapy (28 Gy, delivered through seven 4-Gy doses). Partial remission was achieved after local implantation of iodine-125 (I125) seed under the guidance of a 3D-printed template, with progression-free survival observed up to 8 months afterwards. In conclusion, in patients with PSC who develop superior vena cava blockage after numerous treatment regimens, salvage I125 brachytherapy with a 3D-printed template may be suitable, and may improve local control and symptoms.

Amoxicillin-laded sodium alginate/cellulose nanocrystals/polyvinyl alcohol composite nanonetwork sponges with enhanced wound healing and antibacterial performance.

Wound healing is a complex process and reuires a long repair process. Poor healing effect is normally a challenge for wound healing. Designing sponge dressings with drug-assisted therapy, good breathability, and multiple functional structures effectively promotes wound healing. In this work, a flexible amoxicillin-laded (AMX) sodium alginate (SA)/cellulose nanocrystals (CNCs)/ polyvinyl alcoho (PVA) (SA/CNCs/PVA-AMX, SCP-AMX) wound dressing was designed and built with an excellent porous structure, suitable porosity, and anti-bacterial properties for promoting wound tissue reparation. The porous structure of the wound dressing was fabricated by freeze-thawing cyclic and freeze-dried molding process. This wound dressing exhibited a 3D porous structure for soft-tissue-engineering application, including high porosity (84.2%), swelling ratio (1513%), tensile strength (1.79 MPA), and flexibility. With the inhibition zones of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) being 1.96 and4.58 cm, respectively, this wound dressing demonstrated good antibacterial activity against E. coli and S. aureus. More importantly, wound healing assay in vivo indicates that SCP-AMX could inhibit wound infection, promote collagen deposition, reduce inflammation, and accelerate granulation tissue and wound healing. Thus, the reported wounding dressings present excellent biocompatibility, high antibacterial activities, and excellent biosafety with great potential in wound healing applications.

Nesfatin-1 inhibits cerebral aneurysms by activating Nrf2 and inhibiting NF-κB signaling.

AIMS: Cerebral aneurysm (CA) has been considered one of the most common cerebrovascular diseases, affecting millions of people worldwide. A therapeutic agent is currently missing for the treatment of CA. Nesfatin-1 (Nes-1) is an 82-amino acid adipokine which possesses a wide range of biological functions. However, the physiological function of Nes-1 in CA is still unknown. Here, we aimed to assess the preventive effects of Nes-1 in the pathological development of CA and elucidate the mechanisms behind this. METHODS: We used an elastase-induced CA model, accompanied by a high-salt diet to induce hypertension. Additionally, diverse experimental techniques, including Verhoeff-Van Gieson staining, real time PCR, enzyme-linked immuno sorbent assay (ELISA), and immunofluorescence staining, were employed to assess CA formation, gene and protein expression, as well as the macrophage infiltration. RESULTS: Our results indicate that administration of Nes-1 significantly decreased the aneurysm size. Additionally, Nes-1 prevented inflammatory response by inhibiting the expression of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein 1 (MCP-1) at both the mRNA and protein levels in the Circle of Willis (COW) region. Also, the increased levels of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in the COW region were reduced by Nes-1. We found that Nes-1 administration suppressed the invasion of macrophages. Mechanistically, Nes-1 activated Nrf-2 by promoting its nuclear translocation but prevented the activation of the IκBα/NF-κB signaling pathway. CONCLUSION: These findings suggest that Nes-1 might be used as a promising agent for the prevention of CA.

Association of remnant cholesterol with coronary artery ectasia: a cross-sectional study.

OBJECTIVE: Coronary artery ectasia (CAE) is a condition characterized by the localized or widespread dilation of one or more coronary arteries. The majority of CAE patients do not present with clinical symptoms, and the exact cause of CAE remains unclear. Therefore, a retrospective analysis was conducted to explore the potential causes of CAE. METHODS: This study was a retrospective analysis of patients who underwent coronary angiography at Guangdong Provincial People's Hospital between January 2017 and July 2022, of whom 679 patients were ultimately enrolled in the study. Among them, 260 patients were diagnosed with CAE, whereas 419 patients with normal coronary results composed the control group. Remnant cholesterol (RC) was calculated as total cholesterol (TC) minus high-density lipoprotein cholesterol (HDL-C) minus low-density lipoprotein cholesterol (LDL-C). The association between RC levels and the risk of CAE was assessed via multivariable logistic models. RESULTS: Out of the 679 patients who participated in this study, with an average age of 59.9 years, 38.3% were diagnosed with CAE. Patients with CAE had higher RC levels than did those without CAE (P = 0.001). A significant positive association was observed between RC levels and the risk of CAE, with a multivariable adjusted odds ratio (OR) of 1.950 (95% confidence interval [CI]: 1.163-3.270). There was a significant positive association between RC levels and the risk of CAE in both single-vessel and multivessel dilation cases, as well as in isolated CAE and dilation secondary to coronary atherosclerosis. According to the subgroup analyses, RC levels were positively associated with the risk of CAE in participants with hypertension (OR, 1.065; 95% CI, 1.034-1.098). CONCLUSION: RC levels are positively correlated with CAE, implying that a focus on RC could be beneficial in CAE research.

Construction and application of medication reminder system: intelligent generation of universal medication schedule.

BACKGROUND: Patients with chronic conditions need multiple medications daily to manage their condition. However, most patients have poor compliance, which affects the effectiveness of treatment. To address these challenges, we establish a medication reminder system for the intelligent generation of universal medication schedule (UMS) to remind patients with chronic diseases to take medication accurately and to improve safety of home medication. METHODS: To design medication time constraint with one drug (MTCOD) for each drug and medication time constraint with multi-drug (MTCMD) for each two drugs in order to better regulate the interval and time of patients' medication. Establishment of a medication reminder system consisting of a cloud database of drug information, an operator terminal for medical staff and a patient terminal. RESULTS: The cloud database has a total of 153,916 pharmaceutical products, 496,708 drug interaction data, and 153,390 pharmaceutical product-ingredient pairs. The MTCOD data was 153,916, and the MTCMD data was 8,552,712. An intelligent UMS medication reminder system was constructed. The system can read the prescription information of patients and provide personalized medication guidance with medication timeline for chronic patients. At the same time, patients can query medication information and get remote pharmacy guidance in real time. CONCLUSIONS: Overall, the medication reminder system provides intelligent medication reminders, automatic drug interaction identification, and monitoring system, which is helpful to monitor the entire process of treatment in patients with chronic diseases.

Optimizing medication guidance support for patients with cancer pain: development and evaluation of a pharmaceutical care system for healthcare professionals.

BACKGROUND: Effective management of cancer pain critically depends on timely medication administration and adherence to precise medication guidelines. In the context of limited time and a busy healthcare environment, tailoring the optimal medication schedule for each patient with cancer pain presents a significant challenge for physicians and clinical pharmacists. METHODS: To address this challenge, we conducted a comprehensive analysis of healthcare professionals' needs in guiding cancer pain medication. By developing core features based on key user needs and continuously updating them, we have created the Universal Medication Schedule System (UMSS). We invited 20 physicians and pharmacists specializing in oncology or cancer pain to trial the system and assessed UMSS usage through distributed questionnaires. RESULTS: We identified five key needs of healthcare professionals in cancer pain medication guidance. Based on these needs, we (1) constructed a comprehensive drug information database, including basic information for 1135 drugs, 130,590 drug interaction data entries, and 1409 individual medication timing constraints, and (2) developed a web-based system that provides essential reference information such as drug interactions and dietary restrictions. It can create medication schedules and provide medication education tailored to the patient's daily routine. Participating evaluators unanimously agreed (100%) that the system aids in accurately assessing the risks of polypharmacy and quickly scheduling medication regimens. CONCLUSION: UMSS, by offering personalized medication schedule support, assists healthcare professionals in better managing patients' medication treatment plans. However, further improvements are needed in the automation of database updates and maintenance, as well as in integrating it with electronic health records.

Strategies to overcome the challenges of low or no expression of heterologous proteins in Escherichia coli.

Protein expression is a critical process in diverse biological systems. For Escherichia coli, a widely employed microbial host in industrial catalysis and healthcare, researchers often face significant challenges in constructing recombinant expression systems. To maximize the potential of E. coli expression systems, it is essential to address problems regarding the low or absent production of certain target proteins. This article presents viable solutions to the main factors posing challenges to heterologous protein expression in E. coli, which includes protein toxicity, the intrinsic influence of gene sequences, and mRNA structure. These strategies include specialized approaches for managing toxic protein expression, addressing issues related to mRNA structure and codon bias, advanced codon optimization methodologies that consider multiple factors, and emerging optimization techniques facilitated by big data and machine learning.

Enhancing the stress resistance of nitrile hydratase from Rhodococcus ruber via SpyTag/SpyCatcher-mediated α- and ß- subunits ligation.

BACKGROUND: Nitrile Hydratase (NHase) is one of the most important industrial enzyme widely used in the petroleum exploitation field. The enzyme, composed of two unrelated α- and ß-subunits, catalyzes the conversion of acrylonitrile to acrylamide, releasing a significant amount of heat and generating the organic solvent product, acrylamide. Both the heat and acrylamide solvent have an impact on the structural stability of NHase and its catalytic activity. Therefore, enhancing the stress resistance of NHase to toxic substances is meaningful for the petroleum industry. METHODS AND RESULTS: To improve the thermo-stability and acrylamide tolerance of NHase, the two subunits were fused in vivo using SpyTag and SpyCatcher, which were attached to the termini of each subunit in various combinations. Analysis of the engineered strains showed that the C-terminus of ß-NHase is a better fusion site than the N-terminus, while the C-terminus of α-NHase is the most suitable site for fusion with a larger protein. Fusion of SpyTag and SpyCatcher to the C-terminus of ß-NHase and α-NHase, respectively, led to improved acrylamide tolerance and a slight enhancement in the thermo-stability of one of the engineered strains, NBSt. CONCLUSION: These results indicate that in vivo ligation of different subunits using SpyTag/SpyCatcher is a valuable strategy for enhancing subunit interaction and improving stress tolerance.

Phytoavailability, translocation, and accompanying isotopic fractionation of cadmium in soil and rice plants in paddy fields.

Rice consumption is a major pathway for human cadmium (Cd) exposure. Understanding Cd behavior in the soil-rice system, especially under field conditions, is pivotal for controlling Cd accumulation. This study analyzed Cd concentrations and isotope compositions (δ114/110Cd) in rice plants and surface soil sampled at different times, along with urinary Cd of residents from typical Cd-contaminated paddy fields in Youxian, Hunan, China. Soil water-soluble Cd concentrations varied across sampling times, with δ114/110Cdwater lighter under drained than flooded conditions, suggesting supplementation of water-soluble Cd by isotopically lighter Cd pools, increasing Cd phytoavailability. Both water-soluble Cd and atmospheric deposition contributed to rice Cd accumulation. Water-soluble Cd's contribution increased from 28-52% under flooded to 58-87% under drained conditions due to increased soil Cd phytoavailability. Atmospheric deposition's contribution (12-72%) increased with potential atmospheric deposition flux among sampling areas. The enrichment of heavy Cd isotopes occurred from root-stem-grain to prevent rice Cd accumulation. The different extent of enrichment of heavy isotopes in urine indicated different Cd exposure sources. These findings provide valuable insights into the speciation and phytoavailability changes of Cd in the soil-rice system and highlight the potential application of Cd isotopic fingerprinting in understanding the environmental fate of Cd.

Association between thyroid hormone resistance and obesity: a cross-sectional study and mouse stimulation test.

OBJECTIVE: Thyroid hormone influences key metabolic pathways, and reduced sensitivity to thyroid hormone is considered a new risk factor for adverse metabolic outcomes. However, the association between thyroid hormone resistance and obesity in euthyroid individuals is still unknown. METHODS: We enrolled 8021 euthyroid individuals, calculated thyroid hormone resistance indices, and analyzed the association between thyroid hormone resistance and obesity by regression analysis. Furthermore, we conducted the thyrotropin-releasing hormone stimulation test in both control and obese mice (n = 5) to demonstrate the association. RESULTS: The euthyroid adults with overweight and obesity had increased thyroid hormone resistance indices (all p < 0.05). BMI and prevalence of overweight and obesity increased (odds ratio of thyroid feedback quantile-based index [ORTFQI] = 1.164, p = 0.036; OR of free triiodothyronine/free thyroxine [ORFT3/FT4] = 1.508, p < 0.001) following the elevation of thyroid hormone resistance indices. Mediation analysis indicated a complete mediation effect (beta coefficient of indirect effect [ßInd]= 6.838, p < 0.001) of metabolic disorders in the relationship. Furthermore, in the mice with obesity, the thyrotropin response to thyrotropin-releasing hormone stimulation (68.33-90.89 pg/mL) was comparatively blunted (p = 0.029). CONCLUSIONS: Euthyroid individuals with obesity exhibit both central and peripheral thyroid hormone resistance, a phenomenon that is more pronounced in individuals with metabolic abnormalities. Thyroid hormone resistance is associated with an increased prevalence of overweight and obesity mediated by metabolic disorders.

Analysis of hemorrhagic drug-drug interactions between P-gp inhibitors and direct oral anticoagulants from the FDA Adverse Event Reporting System.

BACKGROUND: Limited understanding exists regarding the hemorrhagic risk resulting from potential interactions between P-glycoprotein (P-gp) inhibitors and direct oral anticoagulants (DOACs). Utilizing the Food and Drug Administration Adverse Event Reporting System (FAERS) data, we analyzed hemorrhagic adverse events (AEs) linked with the co-administration of P-gp inhibitors and DOACs, aiming to offer guidance for their safe and rational use. METHODS: Hemorrhagic events associated with P-gp inhibitors in combination with DOACs were scrutinized from the FAERS database. Hemorrhagic signals mining was performed by estimating the reported odds ratios (RORs), corroborated by additive and multiplicative models and a combination risk ratio (PRR) model. RESULTS: Our analysis covered 4,417,195 cases, revealing 11,967 bleeding events associated with P-gp inhibitors. We observed a significantly higher risk of bleeding with the combination of apixaban and felodipine (ROR 118.84, 95% CI 78.12-180.79, additive model 0.545, multiplicative model 1.253, PRR 22.896 (2450.141)). Moreover, consistent associations were found in the co-administration analyzes of rivaroxaban with dronedarone and diltiazem, and apixaban with losartan, telmisartan, and simvastatin. CONCLUSION: Our FAERS data analysis unveils varying degrees of bleeding risk associated with the co-administration of P-gp inhibitors and DOACs, underscoring the importance of vigilance about them in clinical practice.

125I seed brachytherapy for non-central pelvic recurrence of cervical cancer after external beam radiotherapy.

OBJECTIVE: To investigate the efficacy of 125I seed brachytherapy for non-central pelvic recurrence of cervical cancer after external beam radiotherapy, and to analyze the clinical influential factors. METHODS: Between June 2015 and April 2022, 32 patients with 41 lesions were treated with 125I seed brachytherapy. The seeds were implanted under the guidance of CT and/or 3D-printed template images at a median dose of 100 Gy (range, 80-120 Gy), and the local control rate (LCR) and survival rates were calculated. We used multivariate logistic regression to identify prognosis predictors, and receiver operating characteristic (ROC) curve analysis to determine the optimal cut-off values. RESULTS: The median follow-up was 48.52 months (range, 4-86 months), and the 6-, 12-, and 24-month LCR was 88.0%, 63.2%, and 42.1%, respectively. The 1- and 2-year survival rates were 36% and 33%, respectively, and the median survival time was 13.26 months. No significant adverse events occurred. Multivariate regression analysis showed that tumor diameter, tumor stage, and LCR were independent factors influencing survival. ROC curve analysis showed that the area under the curve for tumor diameter and D90 were 0.765 and 0.542, respectively, with cut-off values of 5.3 cm and 108.5 Gy. CONCLUSIONS: The present findings indicate that 125I seed brachytherapy is feasible for treating non-central pelvic recurrence of cervical cancer after external beam radiotherapy. Further, tumor diameter < 5.3 cm and immediate postoperative D90 > 108.5 Gy were associated with better efficacy.

Wintersweet-like Nanohybrids of Titanium-doped Cerium Vanadate Loaded with Polypyrrole for Tumor Theranostic.

Compromises between enhanced on-targeting reactivity and precise real-time monitoring in the tumor microenvironment (TME) are the main roadblocks for catalytic cancer therapy. The hallmark of a high level of hydrogen peroxide (H2O2) and acidic extracellular environment of the hypoxia solid tumor can underpin therapeutic and tracking performance. Herein, this work provides an activatable wintersweet-like nanohybrid consisting of titanium (Ti) doped cerium vanadate nanorods with the modification of polypyrrole (PPy) nanoparticles (CeVO4-Ti@PPy) for combinatorial therapies of breast carcinoma. The Ti dopants in the size-controllable CeVO4 nanorods lower the energy barrier (0.5 eV) of the rate-determining steps and elaborate peroxidase-like (POD-like) activities to improve the generation of toxic hydroxyl radical (·OH) according to the density functional theory (DFT) calculation. The multiple enzyme-like activities, including the intrinsic glutathione peroxidase (GPx) and catalase (CAT), achieve a record-high therapeutic efficiency. Coupling this oxidative stress with the photothermal effects of PPy enables enhanced catalytic tumor necrosis. The exterior PPy heterogeneous structure can be further doped with protons in the local acidic environment to intensify photoacoustic signals, allowing the non-invasive accurate tracking of tumors. The theranostic performance displayed negligible attenuated signals in near-infrared (NIR) windows. This organic-inorganic nanohybrid with a heterogeneous structure provides the potential to improve the overall outcomes of catalytic therapy.

Revealing the Sources of Cadmium in Rice Plants under Pot and Field Conditions from Its Isotopic Fractionation.

The highly excessive uptake of cadmium (Cd) by rice plants is well known, but the transfer pathway and mechanism of Cd in the paddy system remain poorly understood. Herein, pot experiments and field investigation were systematically carried out for the first time to assess the phytoavailability of Cd and fingerprint its transfer pathway in the paddy system under different treatments (slaked lime and biochar amendments), with the aid of a pioneering Cd isotopic technique. Results unveiled that no obvious differences were displayed in the δ114/110Cd of Ca(NO3)2-extractable and acid-soluble fractions among different treatments in pot experiments, while the δ114/110Cd of the water-soluble fraction varied considerably from -0.88 to -0.27%, similar to those observed in whole rice plant [Δ114/110Cdplant-water ≈ 0 (-0.06 to -0.03%)]. It indicates that the water-soluble fraction is likely the main source of phytoavailable Cd, which further contributes to its bioaccumulation in paddy systems. However, Δ114/110Cdplant-water found in field conditions (-0.39 ± 0.05%) was quite different from those observed in pot experiments, mostly owing to additional contribution derived from atmospheric deposition. All these findings demonstrate that the precise Cd isotopic compositions can provide robust and reliable evidence to reveal different transfer pathways of Cd and its phytoavailability in paddy systems.

A New Isolated Fungus and Its Pathogenicity for Apis mellifera Brood in China.

In this article, we report the pathogenicity of a new strain of fungus, Rhizopus oryzae to honeybee larvae, isolated from the chalkbrood-diseased mummies of honeybee larvae and pupae collected from apiaries in China. Based on morphological observation and internal transcribed spacer (ITS) region analyses, the isolated pathogenic fungus was identified as R. oryzae. Koch's postulates were performed to determine the cause-and-effect pathogenicity of this isolate fungus. The in vitro pathogenicity of this virulent fungus in honeybees was tested by artificially inoculating worker larvae in the lab. The pathogenicity of this new fungus for honeybee larvae was both conidial-concentration and exposure-time dependent; its highly infectious and virulent effect against the larvae was observed at 1 × 105 conidia/larva in vitro after 96 h of challenge. Using probit regression analysis, the LT50 value against the larvae was 26.8 h at a conidial concentration of 1 × 105 conidia/larva, and the LC50 was 6.2 × 103 conidia/larva. These results indicate that the new isolate of R. oryzae has considerable pathogenicity in honeybee larvae. Additionally, this report suggests that pathogenic phytofungi may harm their associated pollinators. We recommend further research to quantify the levels, mechanisms, and pathways of the pathogenicity of this novel isolated pathogen for honeybee larvae at the colony level.

SADR: Self-Supervised Graph Learning With Adaptive Denoising for Drug Repositioning.

Traditional drug development is often high-risk and time-consuming. A promising alternative is to reuse or relocate approved drugs. Recently, some methods based on graph representation learning have started to be used for drug repositioning. These models learn the low dimensional embeddings of drug and disease nodes from the drug-disease interaction network to predict the potential association between drugs and diseases. However, these methods have strict requirements for the dataset, and if the dataset is sparse, the performance of these methods will be severely affected. At the same time, these methods have poor robustness to noise in the dataset. In response to the above challenges, we propose a drug repositioning model based on self-supervised graph learning with adptive denoising, called SADR. SADR uses data augmentation and contrastive learning strategies to learn feature representations of nodes, which can effectively solve the problems caused by sparse datasets. SADR includes an adaptive denoising training (ADT) component that can effectively identify noisy data during the training process and remove the impact of noise on the model. We have conducted comprehensive experiments on three datasets and have achieved better prediction accuracy compared to multiple baseline models. At the same time, we propose the top 10 new predictive approved drugs for treating two diseases. This demonstrates the ability of our model to identify potential drug candidates for disease indications.

A comprehensive exploration of characteristics and source attribution of carbonaceous aerosols in PM2.5 in an East China megacity.

A total of 84 PM2.5 (fine particulate matter) aerosol samples were collected between October 2020 and August 2021 within an urban site in Hangzhou, an East China megacity. Chemical species, such as organic carbon (OC), elemental carbon (EC), as well as char, soot, and n-alkanes, were analyzed to determine their pollution characteristics and source contributions. The mean yearly concentrations of OC, EC, char, soot, and total n-alkanes (∑n-alkane) were 8.76 ± 3.61 µg/m3, 1.44 ± 0.76 µg/m3, 1.21 ± 0.69 µg/m3, 0.3 ± 0.1 µg/m3, and 24.2 ± 10.6 ng/m3. The OC, EC, and ∑n-alkanes were found in the highest levels during winter and lowest during summer. There were strong correlations between OC and EC in both winter and spring, suggesting similar potential sources for these carbonaceous components in both seasons. There were poor correlations among the target pollutants due to summertime secondary organic carbon formation. Potential source contribution functions analysis showed that local pollution levels in winter and autumn were likely influenced by long-range transportation from the Plain of North China. Source index and positive matrix factorization models provided insights into the complex sources of n-alkanes in Hangzhou. Their major contributors were identified as terrestrial plant releases (32.7%), traffic emissions (28.8%), coal combustion (27.3%), and microbial activity (11.2%). Thus, controlling vehicular emissions and coal burning could be key measures to alleviate n-alkane concentrations in the atmosphere of Hangzhou, as well as other Chinese urban centers.

Distribution and sources of polycyclic aromatic hydrocarbons in surface sediments of the East China marginal seas: Significance of the terrestrial input and shelf mud deposition.

To investigate the distribution, sources, influencing factors, and ecological risk of polycyclic aromatic hydrocarbons (PAHs) in East China Marginal Seas (ECMSs) sediments, we measured the concentrations of 16 PAHs in 104 surface sediment samples collected from the ECMSs in 2014 and 2016. Total PAH concentration (∑PAHs) ranged from 4.49 to 163.66 ng/g dry weight (dry w), with 65.98 ± 33.00 (mean ± SD) ng/g dry w. The highest PAH concentrations and total organic carbon were observed in areas with fine-grained sediments in the Bohai Sea (BS), Yellow Sea (YS), and coastal East China Sea (ECS), indicating the prominent influence of regional hydrodynamics and sediment properties. The dominant PAH congener in BS and YS was BbF, whereas coastal ECS was Phe. The heterogeneity of PAH sources implies that terrestrial PAH input and shelf mud deposition have crucial roles in the source-sink processes of PAHs in a strongly human-influenced marginal sea.