Microplastics enhance the adsorption capacity of zinc oxide nanoparticles: Interactive mechanisms and influence factors.

Microplastics (MPs) are of particular concern due to their ubiquitous occurrence and propensity to interact and concentrate various waterborne contaminants from aqueous surroundings. Studies on the interaction and joint toxicity of MPs on engineered nanoparticles (ENPs) are exhaustive, but limited research on the effect of MPs on the properties of ENPs in multi-solute systems. Here, the effect of MPs on adsorption ability of ENPs to antibiotics was investigated for the first time. The results demonstrated that MPs enhanced the adsorption affinity of ENPs to antibiotics and MPs before and after aging showed different effects on ENPs. Aged polyamide prevented aggregation of ZnONPs by introducing negative charges, whereas virgin polyamide affected ZnONPs with the help of electrostatic attraction. FT-IR and XPS analyses were used to probe the physicochemical interactions between ENPs and MPs. The results showed no chemical interaction and electrostatic interaction was the dominant force between them. Furthermore, the adsorption rate of antibiotics positively correlated with pH and humic acid but exhibited a negative correlation with ionic strength. Our study highlights that ENPs are highly capable of accumulating and transporting antibiotics in the presence of MPs, which could result in a widespread distribution of antibiotics and an expansion of their environmental risks and toxic effects on biota. It also improves our understanding of the mutual interaction of various co-existing contaminants in aqueous environments.

Healthcare resource utilization and economic burden of multiple sclerosis in Chinese patients: results from a real-world survey.

Multiple sclerosis (MS) is uncommon in China and the standard of care is underdeveloped, with limited utilization of disease-modifying treatment (DMT). An understanding of real-world disease burden (including direct medical, non-medical, and indirect costs, such as loss of productivity), is currently lacking in this population. To investigate the overall burden of managing patients with MS in China, a cross-sectional survey of physicians and their consulting patients with MS was conducted in 2021. Physicians provided information on healthcare resource utilization (HCRU; consultations, hospitalizations, tests, medication) and associated costs. Patients provided data on changes in their life, productivity, and impairment of daily activities due to MS. Results were stratified by disease severity using generalized linear models, with a p value < 0.05 considered statistically significant. Patients with more severe disease had greater HCRU, including hospitalizations, consultations and tests/scans, and incurred higher direct and indirect costs and productivity loss, compared with those with milder disease. However, the use of DMT was higher in patients with mild disease severity. With the low uptake and limited efficacy of non-DMT drugs, Chinese patients with MS experience a high disease burden and significant unmet needs. Therapeutic interventions could help save downstream costs and lessen societal burden.

Exosomal miRNAs in prenatal diagnosis: Recent advances.

Exosomes, small membranous microvesicles released by cells, contain a range of bioactive molecules, including proteins and miRNAs, which play critical roles in intercellular communication and physiological and pathological processes. Current research suggests that exosomal miRNAs could serve as valuable biomarkers for prenatal diseases, offering a noninvasive method for early detection and monitoring. Studies linking exosomal miRNAs to various birth defects, including fetal growth restriction, urinary tract malformations, cardiovascular system malformations, and hereditary diseases like Down syndrome, were discussed. However, there are some conflicting study findings due to different exosome separation methods. Here, we also discussed exosome separation methods, emphasizing the importance of method selection based on specific purposes and sample types. Further studies are needed to standardize isolation techniques, understand the specific mechanisms underlying exosomal miRNA function, and develop reliable noninvasive prenatal diagnostic indicators. Overall, exosomal miRNAs show promise as potential biomarkers for prenatal diagnosis, but further research is necessary to validate their clinical utility.

Leaching behavior and kinetics of beryllium in beryllium-containing sludge (BCS).

Beryllium-containing sludge (BCS) is a byproduct of the physicochemical treatment of beryllium smelting wastewater. The pollutant element beryllium within BCS is highly unstable and extremely toxic, characterized by its small ionic radius and low charge density, resulting in a high risk of leaching and migration. This study is the first to investigate the leaching behavior, influencing mechanisms, and kinetic processes of beryllium in BCS under various environmental conditions. The results indicate that, under national standard conditions, beryllium exhibits a rapid leaching phase within the first 5 h, which then stabilizes after 10 h, with the total leached content significantly exceeding the leaching toxicity identification standards. Under mildly acidic (pH ≤ 5) or highly alkaline (pH = 14) conditions, beryllium demonstrates pronounced leaching and migration behaviors. Notably, in acidic conditions, the leaching rate exceeds 80% within 5 h. Combining the treatment process of beryllium-containing wastewater with analytical methods such as SEM, XPS, ToF-SIMS, and FTIR, it is revealed that due to the heterogeneous nature of BCS, the particle aggregates dissociate over time under acidic conditions. The particle surfaces become increasingly rough, leading to dissolution and the emergence of more reactive sites, resulting in a high proportion of beryllium leaching. Under these conditions, the gradual reaction of Be(OH)2 in BCS to form soluble Be2+ and its hydrolytic complexes is identified as the primary mechanism for extensive beryllium migration. The process encounters minimal diffusion resistance and is classified as reaction-controlled. In acidic conditions with pH = 4, the leaching rate of beryllium significantly increases with rising temperature. The leaching kinetics equation is [(1-x)-0.44]=e(18.26-53050RT)·t, with an apparent activation energy of 53.05 kJ mol-1.

How should regulatory schemes be optimized to enhance deterrence against medical insurance fraud by enrollees? Evidence from a discrete choice experiment in China.

Medical insurance fraud (MIF) poses a substantial global financial challenge, necessitating effective regulatory strategies, especially in China, where such measures are in a critical developmental phase. This study investigates the effectiveness of various regulatory components in deterring MIF among enrollees and explores preference heterogeneity among individuals with different characteristics, utilizing a discrete choice experiment survey. Grounded in deterrence theory, our conceptual framework incorporates five attributes: intensity of economic penalties, restrictions on medical insurance benefits, deterioration of social reputation, and certainty and celerity of penalties. Employing a D-efficiency design, 24 choice sets were generated and blocked into three versions. A multistage stratified sampling method was adopted to collect data from the basic medical insurance enrollees in Shanghai. The survey was conducted from September to October 2022. The sample representativeness was further improved via the entropy balancing approach. Data from the final sample of 1034 respondents were analyzed using mixed logit models (MIXLs), incorporating interactions with individual characteristics to assess preference heterogeneity. Results reveal that escalating economic penalties, suspending insurance benefits, listing individuals as unfaithful parties, ensuring penalty certainty, and expediting enforcement significantly enhance the deterrent effect. We observed preference heterogeneity across different demographics, including age, gender, education, health status, and employment status. The study underscores the pivotal role of economic penalties in deterring MIF, while also acknowledging the significance of non-economic measures such as enforcement efficiency and social sanctions. These findings offer valuable insights for policymakers to tailor and strengthen regulatory schemes against MIF, contributing to the advancement of more effective and precise healthcare policies.

An unusual presentation of solitary ovarian metastasis from colorectal cancer in an elderly woman: a case report.

Background: There have been cases of colorectal cancer (CRC) metastasizing into the ovary. This study reports a case involving solitary ovarian metastasis (OM) from CRC, which is very rare in the absence of other pelvic and peritoneal metastases. This atypical clinical presentation added to the complexity of the diagnosis. Case Description: We report a case of solitary OM-CRC in a 48-year-old woman. The patient underwent CRC surgery and refused follow-up after three rounds of chemotherapy. Approximately 14 months later, the patient presented with vaginal bleeding for 2 months. The magnetic resonance imaging (MRI) showed a huge solid cystic mass in the right adnexa. Intraoperatively, the right ovary was found to be enlarged and smooth without adhesions. By careful examination of the abdominal cavity, no metastatic lesions were found in the left ovary and uterus, and no seedings were found in the rest of the pelvis and abdomen. After removal of the uterus and bilateral adnexa, the histologic examination revealed metastatic adenocarcinoma of the right ovary with a considered rectal carcinoma of origin. Positive staining for multiple tumor-associated markers, which further established the primary nature of CRC. These findings support a possible diagnosis of primary CRC and ovarian metastases. The patient recovered well after the operation and no recurrence or metastasis was seen 18 months after the operation. Conclusions: Solitary ovarian metastases from CRC can be better managed and treated by increasing clinicians' vigilance for this rare condition. This helps to improve the patient's prognosis and quality of life.

Enhanced immune reconstitution with albuvirtide in HIV-infected immunological non-responders.

Background: Incomplete immune recovery in people living with HIV/AIDS (PLWHA) remains an important clinical challenge with the lack of an effective strategy currently available to restore their T-cell immune response. This study aimed to evaluate the effect of Albuvirtide (ABT) on immune recovery in immunological non-responders (INRs) and attempted to explore potential mechanisms of ABT on the functionality of immune cells. Methods: In this prospective, open-label, controlled clinical study, participants with incomplete immune reconstitution (continuous ART over 5 years and CD4+T lymphocyte absolute count of <500 cells/µl or ART for 2-5 years and CD4+T cell count of <200 cells/µl with undetectable viral load) were received intensive treatment with ABT or maintained on the original ART regimen at a ratio of 1:1. Immune response and safety were examined within 24 weeks. In the cytological study, T subsets, cell apoptosis and cell autophagy were analyzed using immunofluorescence staining and flow cytometry from 25 blood specimens. Results: Both groups (n=25 each) were comparable in age, gender, and ART duration. At week 12, CD4+T cell count increased significantly in the intensive ABT group compared with control group (the change from baseline in CD4+T cell count: 45 vs. -5 cells/µL, p<0.001). After ABT discontinuation, CD4+T cell counts remained significantly higher in the intensive ABT group at week 24 (55 vs. -5 cells/µL, p=0.012). In laboratory analysis, naïve CD4+ T cell amounts were lowest among participants with unsatisfactory immune response (uIR) to ABT (p=0.001). The proportion of caspase 3+CD45RA+CD31+CD4+ T cells was significantly lower in participants with satisfactory immune response (sIR) to ABT (p<0.05). Conclusion: Significant CD4+T cell count increase suggests ABT enhances immune function in INRs which may be attributed to its antiviral properties as well as its ability to increase thymic cell output and decrease cell apoptosis.

The effects of sequencing strategies on Metagenomic pathogen detection using bronchoalveolar lavage fluid samples.

Objectives: Metagenomic next-generation sequencing (mNGS) is a powerful tool for pathogen detection. The accuracy depends on both wet lab and dry lab procedures. The objective of our study was to assess the influence of read length and dataset size on pathogen detection. Methods: In this study, 43 clinical BALF samples, which tested positive via clinical mNGS and were consistent with the diagnosis, were subjected to re-sequencing on the Illumina NovaSeq 6000 platform. The raw re-sequencing data, consisting of 100 million (M) paired-end 150 bp (PE150) reads, were divided into simulated datasets with eight different data sizes (5 M, 10 M, 15 M, 20 M, 30 M, 50 M, 75 M, 100 M) and five different read lengths (single-end 50 bp (SE50), SE75, SE100, PE100, and PE150). Both Kraken2 and IDseq bioinformatics pipelines were employed to analyze the previously diagnosed pathogens in the simulated data. Detection of pathogens was based on read counts ranging from 1 to 10 and RPM values ranging from 0.2 to 2. Results: Our results revealed that increasing dataset sizes and read lengths can enhance the performance of mNGS in pathogen detection. However, a larger data sizes for mNGS require higher economic costs and longer turnaround time for data analysis. Our findings indicate 20 M reads being sufficient for SE75 mode to achieve high recall rates. Additionally, high nucleic acid loads in samples can lead to increased stability in pathogen detection efficiency, reducing the impact of sequencing strategies. The choice of bioinformatics pipelines had a significant impact on recall rates achieved in pathogen detection. Conclusions: Increasing dataset sizes and read lengths can enhance the performance of mNGS in pathogen detection but increase the economic and time costs of sequencing and data analysis. Currently, the 20 M reads in SE75 mode may be the best sequencing option.

Effect and mechanism of Jinkui Shenqi Pill on preventing neural tube defects in mice based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: jinkui Shenqi Pill (JSP) is a classic traditional Chinese medicine used to treat "Kidney Yang Deficiency" disease. Previous studies indicate a protective effect of JSP on apoptosis in mouse neurons. AIM OF THE STUDY: This research, combining network pharmacology with in vivo experiments, explores the mechanism of JSP in preventing neural tube defects (NTDs) in mice. MATERIALS AND METHODS: Network pharmacology analyzed JSP components and targets, identifying common genes with NTDs and exploring potential pathways. Molecular docking assessed interactions between key JSP components and pathway proteins. In an all-trans retinoic acid (atRA)-induced NTDs mouse model, histopathological changes were observed using HE staining, neuronal apoptosis was detected using TUNEL, and Western Blot assessed changes in the PI3K/AKT signaling pathway and apoptosis-related proteins. RESULTS: Different concentrations of JSP led to varying degrees of reduction in the occurrence of neural tube defects in mouse embryos, with the highest dose showing the most significant decrease. Furthermore, it showed a better reduction in NTDs rates compared to folic acid (FA). Network pharmacology constructed a Drug-Active Ingredient-Gene Target network, suggesting key active ingredients such as Quercetin, Wogonin, Beta-Sitosterol, Kaempferol, and Stigmasterol, possibly acting on the PI3K/Akt signaling pathway. Molecular docking confirmed stable binding structures. Western Blot analysis demonstrated increased expression of p-PI3K, p-Akt, p-Akt1, p-Akt2, p-Akt3, downregulation of cleaved caspase-3 and Bax, and upregulation of Bcl-2, indicating prevention of NTDs through anti-apoptotic effects. CONCLUSION: We have identified an effective dosage of JSP for preventing NTDs, revealing its potential by activating the PI3K/Akt signaling pathway and inhibiting cell apoptosis in atRA-induced mouse embryonic NTDs.

Effects of nitrogen application on ammonium assimilation and microenvironment in the rhizosphere of drip-irrigated sunflower under plastic mulch.

This study investigated the effect of nitrogen application on the rhizosphere soil microenvironment of sunflower and clarified the relationship between ammonium assimilation and the microenvironment. In a field experiment high (HN, 190 kg/hm2), medium (MN, 120 kg/hm2) and low nitrogen (CK, 50 kg/hm2) treatments were made to replicate plots of sunflowers using drip irrigation. Metagenomic sequencing was used to analyze the community structure and functional genes involved in the ammonium assimilation pathway in rhizosphere soil. The findings indicated that glnA and gltB played a crucial role in the ammonium assimilation pathway in sunflower rhizosphere soil, with Actinobacteria and Proteobacteria being the primary contributors. Compared with CK treatment, the relative abundance of Actinobacteria increased by 15.57% under MN treatment, while the relative abundance decreased at flowering and maturation stages. Conversely, the relative abundance of Proteobacteria was 28.57 and 61.26% higher in the MN treatment during anthesis and maturation period, respectively, compared with the CK. Furthermore, during the bud stage and anthesis, the abundance of Actinobacteria, Proteobacteria, and their dominant species were influenced mainly by rhizosphere soil EC, ammonium nitrogen (NH4+-N), and nitrate nitrogen (NO3--N), whereas, at maturity, soil pH and NO3--N played a more significant role in shaping the community of ammonium-assimilating microorganisms. The MN treatment increased the root length density, surface area density, and root volume density of sunflower at the bud, flowering, and maturity stages compared to the CK. Moreover, root exudates such as oxalate and malate were positively correlated with the dominant species of Actinobacteria and Proteobacteria during anthesis and the maturation period. Under drip irrigation, applying 120 kg/hm2 of nitrogen to sunflowers effectively promoted the community structure of ammonium-assimilating microorganisms in rhizosphere soil and had a positive influence on the rhizosphere soil microenvironment and sunflower root growth.

Delivery of neurotrophin-3 by RVG-Lamp2b-modified mesenchymal stem cell-derived exosomes alleviates facial nerve injury.

We aim to investigate the effect of RVG-Lamp2b-modified exosomes (exos) loaded with neurotrophin-3 (NT-3) on facial nerve injury. Exos were collected from control cells (Ctrl Exo) or bone marrow mesenchymal stem cells co-transfected with RVG-Lamp2b and NT-3 plasmids (RVG-NT-3 Exo) by gradient centrifugation and identified by western blotting, transmission electron microscopy, and nanoparticle tracking analysis. Effect of RVG-NT-3 Exo on oxidative stress damage was determined by analysis of the morphology, viability, and ROS production of neurons. Effect of RVG-NT-3 Exo on facial nerve axotomy (FNA) was determined by detecting ROS production, neuroinflammatory reaction, microglia activation, facial motor neuron (FMN) death, and myelin sheath repair. Loading NT-3 and modifying with RVG-Lamp2b did not alter the properties of the exos. Moreover, RVG-NT-3 Exo could effectively target neurons to deliver NT-3. Treatment with RVG-NT-3 Exo lowered H2O2-induced oxidative stress damage in primary neurons and Nsc-34 cells. RVG-NT-3 Exo treatment significantly decreased ROS production, neuroinflammatory response, FMN death, and elevated microglia activation and myelin sheath repair in FNA rat models. Our findings suggested that RVG-NT-3 Exo-mediated delivery of NT-3 is effective for the treatment of facial nerve injury.

Clinical predictors of severe radiation pneumonitis in patients undergoing thoracic radiotherapy for lung cancer.

Background: Severe radiation pneumonitis (RP), one of adverse events in patients with lung cancer receiving thoracic radiotherapy, is more likely to lead to more mortality and poor quality of life, which could be predicted by clinical information and treatment scheme. In this study, we aimed to explore the clinical predict model for severe RP. Methods: We collected information on lung cancer patients who received radiotherapy from August 2020 to August 2022. Clinical features were obtained from 690 patients, including baseline and treatment data as well as radiation dose measurement parameters, including lung volume exceeding 5 Gy (V5), lung volume exceeding 20 Gy (V20), lung volume exceeding 30 Gy (V30), mean lung dose (MLD), etc. Among them, 621 patients were in the training cohort, and 69 patients were in the test cohort. Three models were built using different screening methods, including multivariate logistics regression (MLR), backward stepwise regression (BSR), and random forest regression (RFR), to evaluate their predictive power. Overoptimism in the training cohorts was evaluated by four validation methods, including hold-out, 10-fold, leave-one-out, and bootstrap methods, and test cohort was used to evaluate the predictive performance of the model. Model calibration, decision curve analysis (DCA), and evaluation of the nomograms for the three models were completed. Results: Severe RP was up to 9.4%. The results of multivariate analysis of logistics regression in all patients showed that patients with subclinical (untreated and asymptomatic) interstitial lung disease (ILD) could increase the risk of severe RP, and patients with a better lung diffusion function and received standardized steroids treatment could decrease the risk of severe RP. The three models built by MLR, BSR, and RFR all had good accuracy (>0.850) and moderate κ value (>0.4), and the model 2 built by BSR had the highest area under the receiver operating characteristic (ROC) curve (AUC) in three models, which was 0.958 [95% confidence interval (CI): 0.932-0.985]. The calibration curve showed good agreement between the predicted and actual values, and the DCA showed a positive net benefit for the model 2 which drew the nomogram. The model 2 included subclinical ILD, diffusing capacity of the lung for carbon monoxide (DLCO), ipsilateral lung V20, and standardized steroid treatment, which could affect the incidence of severe RP. Conclusions: Subclinical ILD, DLCO, ipsilateral lung V20, and with or not standardized steroid treatment could affect the incidence of severe RP. Strict lung dose limitation and standardized steroid treatment could contribute to a decrease in severe RP.

Identification and evaluation of a six-lncRNA prognostic signature for multiple myeloma.

PURPOSE: Multiple myeloma (MM) is the second most common hematologic malignancy, and there is no cure for this disease. This study aimed to explore the prognostic value of long noncoding RNAs (lncRNAs) in MM and to reveal related immune and chemotherapy resistance mechanisms. METHODS: In this study, lncRNA profiles from the Multiple Myeloma Research Foundation (MMRF) and Gene Expression Omnibus (GEO) databases were analyzed to identify lncRNAs linked to MM patient survival. A risk assessment model stratified patients into high- and low-risk groups, and survival was evaluated. Additionally, a triple-ceRNA (lncRNA-miRNA-mRNA) network was constructed, and functional analysis was performed. The research also involved immune function analysis and chemotherapy drug sensitivity assessment using oncoPredict and the GDSC dataset. RESULTS: We identified 422 lncRNAs significantly associated with overall survival in MM patients and ultimately focused on the 6 with the highest prognostic value. These lncRNAs were used to develop a risk score formula that stratified patients into high- and low-risk groups. Kaplan-Meier analysis revealed shorter survival in high-risk patients. We integrated this lncRNA signature with clinical parameters to construct a nomogram for predicting MM prognosis. Additionally, a triple-ceRNA network was constructed to reveal potential miRNA targets, coding genes related to these lncRNAs and significantly enriched pathways. Immune checkpoint gene expression and immune cell composition were also analyzed in relation to the lncRNA risk score. Finally, using the oncoPredict tool, we observed that high-risk patients exhibited decreased sensitivity to key MM chemotherapeutics, suggesting that lncRNA profiles are linked to chemotherapy resistance.

APTT critical value establishment in four different reagent/instrument systems based on single factor deficiencies.

INTRODUCTION: There are significant differences in the activated partial thromboplastin time (APTT) critical values reported in different studies, most of which does not make recommendations for any specific clear detection systems. The International Council for Standardization in Hematology (ICSH) recommends that APTT critical values be established based on the reagent type, coagulation factor sensitivity and heparin response. The objective of this study was to establish APTT critical values by using different reagents and based on single coagulation factor deficiencies. METHODS: The APTT values were determined in commercial endogenous coagulation factor-deficient plasma at concentrations of 1 IU/dL, 2 IU/dL, 5 IU/dL, 10 IU/dL, 20 IU/dL, and 30 IU/dL by using four assay systems. The retrospective collection of data from patients who lacked factor VIII (FVIII), FIX, or FXI alone was performed. Receiver operating characteristic (ROC) curves were constructed to assess the diagnostic accuracy of APTT for identifying patients with an endogenous coagulation factor activity < 5 IU/dL. RESULTS: The APTT values in the plasma samples with the same concentrations of endogenous coagulation factors were significantly different among the four assay systems (P < 0.001). The suggested critical values of APTT were 40.0 s for Sysmex CS5100 (Actin FSL), 58.0 s for Sysmex CS5100 (Actin), 51.8 s for STA-R Evolution (STA-PTTA), and 64.8 s for ACL TOP 700 (HemosIL SynthasIL). On the basis of the ROC curve, the optimal threshold values for APTT (STA-PTTA) were 55.8 s in patients with a simple deficiency of FVIII (sensitivity = 100%, specificity = 85.7%, area under the ROC curve (AUC) = 0.982), 54.3 s in patients with a simple deficiency of FIX (sensitivity = 100%, specificity = 92.9%, AUC = 0.986), and 71.7 s in patients with a simple deficiency of FXI (sensitivity = 100%, specificity = 94.1%, AUC = 0.992), which were closer (difference of 0.6-2.5 s) to the cutoff points for commercial plasma at equal factor levels. CONCLUSIONS: APTT critical values need to be established for different reagents based on the presence of a single coagulation factor deficiency.

The protective mechanism of human umbilical cord mesenchymal stem cell-derived exosomes against neutrophil extracellular trap-induced placental damage.

INTRODUCTION: Preeclampsia (PE) is a pregnancy-specific complication. Its etiology and pathogenesis remain unclear. Previous studies have shown that neutrophil extracellular traps (NETs) cause placental dysfunction and lead to PE. Human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-EXOs) have been widely used to treat different diseases. We investigated whether hUCMSC-EXOs can protect against NET-induced placental damage. METHODS: NETs were detected in the placenta by immunofluorescence. The impact of NETs on cellular function and the effect of hUCMSC-EXOs on NET-induced placental damage were evaluated by 5-ethynyl-20-deoxyuridine (EdU) cell proliferation, lactate dehydrogenase (LDH), reactive oxygen species (ROS), and cell migration, invasion and tube formation assays; flow cytometry; and Western blotting. RESULTS: The number of placental NETs was increased in PE patients compared with control individuals. NETs impaired the function of endothelial cells and trophoblasts. These effects were partially reversed after N-acetyl-L-cysteine (NAC; ROS inhibitor) or DNase I (NET lysing agent) pretreatment. HUCMSC-EXOs ameliorated NET-induced functional impairment of endothelial cells and trophoblasts in vitro, partially reversed NET-induced inhibition of endothelial cell and trophoblast proliferation, and partially restored trophoblast migration and invasion and endothelial cell tube formation. Exosomes inhibited ROS production in these two cell types, suppressed p38 mitogen-activated protein kinase (p38 MAPK) signaling activation, activated extracellular signal-regulated kinase 1/2 (ERK1/2) signaling, and modulated the Bax, Bim, Bcl-2 and cleaved caspase-3 levels to inhibit apoptosis. DISCUSSION: HUCMSC-EXOs can reverse NET-induced placental endothelial cell and trophoblast damage, possibly constituting a theoretical basis for the treatment of PE with exosomes.

Controlling factors of heavy metal(loid) accumulation in rice: Main and interactive effects.

Identifying the key determinants of heavy metal(loid) accumulation in rice and quantifying their contributions are critical for precise prediction of heavy metal(loid) concentrations in rice and the formulation of effective pollution control strategies. The accumulation of heavy metal(loid)s in rice can be influenced by both natural and anthropogenic factors, which may interact with each other. However, distinguishing the independent roles (main effects) from interactive effects and quantifying their impacts separately pose challenges. To address this knowledge gap, we employed TreeExplainer-based SHAP and random forest algorithms in this study to quantitatively estimate the primary influencing factors and their main and interactive effects on heavy metal(loid)s in rice. Our findings reveal that soil cadmium (SCd) and rice cultivation time (C_TIME) were the primary contributors to rice cadmium (RCd) and rice arsenic (RAs), respectively. Soil lead (SPb) and sampling distances from roads significantly contributed to rice lead (RPb). Additionally, we identified significant interactive effects of SCd and C_TIME, C_TIME and RCd, and RCd and rice variety on RCd, RAs, and RPb, respectively, emphasizing their significance. These insights are pivotal in improving the accuracy of heavy metal(loid) concentration predictions in rice and offering theoretical guidance for the formulation of pollution control measures.

The sweating process promotes toxigenic fungi expansion and increases the risk of combined contamination of mycotoxins in Radix Dipsaci.

Sweating is one of the most important processing methods of Chinese medicinal herbs. However, the high temperature and humidity environment required for sweating Chinese medicinal herbs makes it very easy for fungi to breed, especially toxigenic fungi. The mycotoxins produced by these fungi will then contaminate the Chinese medicinal herbs. In this study, we explored the changes in mycobiota, toxigenic fungi, and mycotoxins with and without sweating in Radix Dipsaci (RD), a typical representative of traditional Chinese medicine that requires processing through sweating. We also isolated and identified the toxigenic fungi from RD, whether they were subjected to sweating treatment or not, and examined their toxigenic genes and ability. The results showed that the detection rate of mycotoxins (aflatoxins, ochratoxins, zearalenone, and T-2 toxin) in RD with sweating was 36%, which was 2.25-fold higher than that in RD without sweating. We also detected T-2 toxin in the RD with sweating, whereas it was not found in the RD without sweating. The sweating process altered the fungal composition and increased the abundance of Fusarium and Aspergillus in RD. Aspergillus and Fusarium were the most frequently contaminating fungi in the RD. Morphological and molecular identification confirmed the presence of key toxigenic fungal strains in RD samples, including A. flavus, A. westerdijkiae, F. oxysporum and F. graminearum. These four fungi, respectively, carried AflR, PKS, Tri7, and PKS14, which were key genes for the biosynthesis of aflatoxins, ochratoxins, zearalenone, and T-2 toxin. The toxigenic ability of these four fungal strains was verified in different matrices. We also found that A. flavus, A. westerdijkiae, and F. oxysporum were isolated in RD both with sweating and without sweating, but their isolation frequency was significantly higher in the RD with sweating than in the RD without sweating. F. graminearum was not isolated from RD without sweating, but it was isolated from RD with sweating. These findings suggest that the sweating process promotes the expansion of toxigenic fungi and increases the risk of combined mycotoxin contamination in RD.

Ozone sensitivity regimes vary at different heights in the planetary boundary layer.

The sensitivity of tropospheric ozone (O3) to its precursors volatile organic compounds (VOCs) and nitrogen oxides (NOX) determines the emission reduction strategy for O3 mitigation. Due to the lack of comprehensive vertical measurements of VOCs, the vertical distribution of O3 sensitivity regimes has not been well understood. O3 precursor sensitivity determined by ground-level measurements has been generally used to guide O3 control strategy. Here, to precisely diagnose O3 sensitivity regimes at different heights in the planetary boundary layer (PBL), we developed a vertical measurement system based on an unmanned aerial vehicle platform to conduct comprehensive vertical measurements of VOCs, NOX and other relevant parameters. Our results suggest that the O3 precursor sensitivity shifts from a VOC-limited regime at the ground to a NOX-limited regime at upper layers, indicating that the ground-level O3 sensitivity cannot represent the situation of the whole PBL. We also found that the state-of-the-art photochemical model tends to underestimate oxygenated VOCs at upper layers, resulting in overestimation of the degree of VOCs-limited regime. Therefore, thorough vertical measurements of VOCs to accurately diagnose O3 precursor sensitivity is in urgent need for the development of effective O3 control strategies.

A joint population pharmacokinetic model to assess the high variability of whole-blood and intracellular tacrolimus in early adult renal transplant recipients.

Tacrolimus (TAC) has high pharmacokinetic (PK) variability during the early transplantation period. The relationships between whole-blood and intracellular TAC concentrations and clinical outcomes remain controversial. This study identifies the factors affecting the PK variability of TAC and characterizes the relationships between whole-blood and intracellular TAC concentrations. Data regarding whole-blood TAC concentrations of 1,787 samples from 215 renal transplant recipients (<90 days postoperative) across two centers and intracellular TAC concentrations (648 samples) digitized from previous studies were analyzed using nonlinear mixed-effects modeling. The effects of potential covariates were screened, and the distribution of whole-blood to intracellular TAC concentration ratios (RWB:IC) was estimated. The final model was evaluated using bootstrap, goodness of fit, and prediction-corrected visual predictive checks. The optimal dosing regimens and target ranges for each type of immune cell subsets were determined using Monte Carlo simulations. A two-compartment model adequately described the data, and the estimated mean TAC CL/F was 23.6 L·h-1 (relative standard error: 11.5 %). The hematocrit level, CYP3A5*3 carrier status, co-administration with Wuzhi capsules, and tapering prednisolone dose may contribute to the high variability of TAC PK variability during the early post-transplant period. The estimated RWB:IC of all TAC concentrations in peripheral blood mononuclear cells (PBMCs) was 4940, and inter-center variability of PBMCs was observed. The simulated TAC target range in PBMCs was 20.2-85.9 pg·million cells-1. Inter-center variability in intracellular concentrations should be taken into account in further analyses. TAC dosage adjustments can be guided based on PK/PD variability and simulated intracellular concentrations.