Efficient Extraction and Analysis of Nanoplastics by Ionic Liquid-Assisted Cloud-Point Extraction Coupled with Electromagnetic Heating Pyrolysis Mass Spectrometry.

Nanoplastics have attracted much attention due to their potential hazards. However, analysis of nanoplastics remains challenging. In this study, ionic liquid-assisted cloud-point extraction (IL-assisted CPE) was developed to enrich nanoplastics in the aqueous environment and further coupled with electromagnetic heating pyrolysis mass spectrometry. The use of trace ILs improves the extraction efficiency of CPE for nanoplastics. The effects of ILs (types, contents), nanoplastic properties (type, size), and environmental factors (aging time, humic acid content) were systematically investigated to evaluate the applicability. The limits of detection of poly(methyl methacrylate) (PMMA) and polystyrene (PS) were determined to be 1.78 and 2.67 µg/L, respectively. Real environmental samples including lake water, rainwater, and influent and effluent from wastewater treatment plant were analyzed with good accuracy (79.58-116.87%) and satisfactory precision (RSD ≤ 11.99%). A possible mechanism for ILs being absorbed into the ordered surfactant micellar and generating larger micelles to synergically enclose hydrophobic nanoplastics was proposed. This work provides a simple and efficient approach to the extraction and analysis of nanoplastics in aqueous environments.

The nematode effector calreticulin competes with the high mobility group protein OsHMGB1 for binding to the rice calmodulin-like protein OsCML31 to enhance rice susceptibility to Meloidogyne graminicola.

The root-knot nematode Meloidogyne graminicola secretes effectors into rice tissues to modulate host immunity. Here, we characterised MgCRT1, a calreticulin protein of M. graminicola, and identified its target in the plant. In situ hybridisation showed MgCRT1 mRNA accumulating in the subventral oesophageal gland in J2 nematodes. Immunolocalization indicated MgCRT1 localises in the giant cells during parasitism. Host-induced gene silencing of MgCRT1 reduced the infection ability of M. graminicola, while over-expressing MgCRT1 enhanced rice susceptibility to M. graminicola. A yeast two-hybrid approach identified the calmodulin-like protein OsCML31 as an interactor of MgCRT1. OsCML31 interacts with the high mobility group protein OsHMGB1 which is a conserved DNA binding protein. Knockout of OsCML31 or overexpression of OsHMGB1 in rice results in enhanced susceptibility to M. graminicola. In contrast, overexpression of OsCML31 or knockout of OsHMGB1 in rice decreases susceptibility to M. graminicola. The GST-pulldown and luciferase complementation imaging assay showed that MgCRT1 decreases the interaction of OsCML31 and OsHMGB1 in a competitive manner. In conclusion, when M. graminicola infects rice and secretes MgCRT1 into rice, MgCRT1 interacts with OsCML31 and decreases the association of OsCML31 with OsHMGB1, resulting in the release of OsHMGB1 to enhance rice susceptibility.

Context-dependent T-BOX transcription factor family: from biology to targeted therapy.

T-BOX factors belong to an evolutionarily conserved family of transcription factors. T-BOX factors not only play key roles in growth and development but are also involved in immunity, cancer initiation, and progression. Moreover, the same T-BOX molecule exhibits different or even opposite effects in various developmental processes and tumor microenvironments. Understanding the multiple roles of context-dependent T-BOX factors in malignancies is vital for uncovering the potential of T-BOX-targeted cancer therapy. We summarize the physiological roles of T-BOX factors in different developmental processes and their pathological roles observed when their expression is dysregulated. We also discuss their regulatory roles in tumor immune microenvironment (TIME) and the newly arising questions that remain unresolved. This review will help in systematically and comprehensively understanding the vital role of the T-BOX transcription factor family in tumor physiology, pathology, and immunity. The intention is to provide valuable information to support the development of T-BOX-targeted therapy.

Advances in researches on long coronavirus disease in children: a narrative review.

Background and Objective: In the context of the global pandemic of coronavirus disease 2019 (COVID-19), more than 700 million infections and millions of deaths have occurred in countries around the world. Currently, two main sequelae of this disease are considered to occur in children, namely, multi-system inflammatory syndrome in children and long COVID. Among these two, the incidence of long COVID is higher and its impact on the population is more extensive, which is the focus of us. However, due to the lack of relevant studies and the limitations of most studies, the studies on sequelae of COVID-19 infection lag behind those of adults, but they have begun to attract the attention of some clinicians and researchers. We aim to summarize the current knowledge of long COVID in children, helping pediatricians and researchers to better understand this disease and providing guidance on research and clinical treatment of it. Methods: We reviewed all the studies on "long COVID", pediatric, children, adolescent, post-COVID syndrome in PubMed published after 2019. Key Content and Findings: This review summarizes the latest researches on epidemiology, pathogenesis, clinical manifestations, prevention and treatment of long COVID in children. Based on the existing research data, we summarized and analyzed the characteristics of long COVID in children, discovering the means to decipher the diagnosis of COVID-19 in children and some potential therapeutic treatments. Conclusions: We aim to summarize existing research on long COVID in children and help pediatricians and government agencies quickly understand the disease so that it can be used for clinical diagnosis, treatment and prevention in the population. In addition, providing a research basis for further researches on the cellular and even molecular level to explain the occurrence and development of diseases, and has a guiding role for future research direction.

Cumulative sum learning curve analysis of tubularized incised plate repair for hypospadias: a study of a single surgeon with a single surgical procedure.

Purpose: To ascertain the quantity of instances by which a single surgeon achieves competency and proficiency in using tubularized incised plate (TIP) technique for the repair of distal and mid-shaft hypospadias using the cumulative sum (CUSUM) analysis. Methods: We retrospectively evaluated patients with distal and mid-shaft hypospadias who were treated by a single surgeon between 2015 and 2021, using a single primary TIP technique with a de-epithelialized Byars flap. Data including type of hypospadias, age at surgery, curvature, operation time (OT), length of the reconstructed urethra, and postoperative outcomes were collected and assessed. CUSUM was used to assess the trends in OT and complication rate (CR) in order to generate the learning curve. The evolution of OT and CR can be divided into three phases: learning, competence, and proficiency. Results: CUSUM identified three phases in the learning curves of all TIP repairs. The median OT decreased from 135 min [interquartile range (IQR) = 125-155] to 92 min (IQR = 80-100) (P < 0.001), CR decreased from 28 (28%) to 8 (5.3%) (P < 0.001), and reoperations decreased from 15 (15.2%) to 4 (2.6%) (P < 0.001). According to the CUSUM learning curve, technical competency plateaued after the 99th case, and both OT and CR entered a significantly declining proficiency phase after the 231st case. Further, when the neourethral length exceeded the total average, total complications, urethrocutaneous fistula, and reoperations increased (P = 0.013, P = 0.006, and P = 0.028, respectively). Conclusions: Our study suggests that surgeons performing TIP repair may reach technical competency and achieve proficiency after operating on 99,231 cases, respectively. Moreover, the longer the neourethral length, the higher is the CR.

The switch triggering the invasion process: Lipid metabolism in the metastasis of hepatocellular carcinoma.

ABSTRACT: In humans, the liver is a central metabolic organ with a complex and unique histological microenvironment. Hepatocellular carcinoma (HCC), which is a highly aggressive disease with a poor prognosis, accounts for most cases of primary liver cancer. As an emerging hallmark of cancers, metabolic reprogramming acts as a runaway mechanism that disrupts homeostasis of the affected organs, including the liver. Specifically, rewiring of the liver metabolic microenvironment, including lipid metabolism, is driven by HCC cells, propelling the phenotypes of HCC cells, including dissemination, invasion, and even metastasis in return. The resulting formation of this vicious loop facilitates various malignant behaviors of HCC further. However, few articles have comprehensively summarized lipid reprogramming in HCC metastasis. Here, we have reviewed the general situation of the liver microenvironment and the physiological lipid metabolism in the liver, and highlighted the effects of different aspects of lipid metabolism on HCC metastasis to explore the underlying mechanisms. In addition, we have recapitulated promising therapeutic strategies targeting lipid metabolism and the effects of lipid metabolic reprogramming on the efficacy of HCC systematical therapy, aiming to offer new perspectives for targeted therapy.

Augmenting regulatory T cells: new therapeutic strategy for rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune condition marked by inflammation of the joints, degradation of the articular cartilage, and bone resorption. Recent studies found the absolute and relative decreases in circulating regulatory T cells (Tregs) in RA patients. Tregs are a unique type of cells exhibiting immunosuppressive functions, known for expressing the Foxp3 gene. They are instrumental in maintaining immunological tolerance and preventing autoimmunity. Increasing the absolute number and/or enhancing the function of Tregs are effective strategies for treating RA. This article reviews the studies on the mechanisms and targeted therapies related to Tregs in RA, with a view to provide better ideas for the treatment of RA.

ASM is a therapeutic target in dermatomyositis by regulating the differentiation of naive CD4 + T cells into Th17 and Treg subsets.

BACKGROUND: This study aims to investigate the involvement of acid sphingomyelinase (ASM) in the pathology of dermatomyositis (DM), making it a potential therapeutic target for DM. METHODS: Patients with DM and healthy controls (HCs) were included to assess the serum level and activity of ASM, and to explore the associations between ASM and clinical indicators. Subsequently, a myositis mouse model was established using ASM gene knockout and wild-type mice to study the significant role of ASM in the pathology and to assess the treatment effect of amitriptyline, an ASM inhibitor. Additionally, we investigated the potential treatment mechanism by targeting ASM both in vivo and in vitro. RESULTS: A total of 58 DM patients along with 30 HCs were included. The ASM levels were found to be significantly higher in DM patients compared to HCs, with median (quartile) values of 2.63 (1.80-4.94) ng/mL and 1.64 (1.47-1.96) ng/mL respectively. The activity of ASM in the serum of DM patients was significantly higher than that in HCs. Furthermore, the serum levels of ASM showed correlations with disease activity and muscle enzyme levels. Knockout of ASM or treatment with amitriptyline improved the severity of the disease, rebalanced the CD4 T cell subsets Th17 and Treg, and reduced the production of their secreted cytokines. Subsequent investigations revealed that targeting ASM could regulate the expression of relevant transcription factors and key regulatory proteins. CONCLUSION: ASM is involved in the pathology of DM by regulating the differentiation of naive CD4 + T cells and can be a potential treatment target.

Detection of nanoplastics released from consumer plastic food containers by electromagnetic heating pyrolysis mass spectrometry.

Nanoplastics released from consumer plastic food containers are emerging environmental pollutants and directly ingested as part of the diet. However, quantification methods for nanoplastics are still lacking. Herein, a rapid identification and mass quantification approach was developed for nanoplastics analysis by combining electromagnetic heating with pyrolysis mass spectrometry (Eh-Py-MS). The pyrolysis products directly entered into the MS, which omits the gas phase separation process and shortens the detection time. A compact pyrolysis chamber was used and this increased the sample transfer efficiency and lowered power requirement. The operational parameters were systematically examined. The influence of nanoplastic size, additive, humic acid, and aging on detection was investigated, and it was concluded that environmental factors (humic acid, aging) and plastic properties (size, additives) did not influence the detection. The developed chamber showed that the limit of detection of polystyrene (PS) nanoplastics was 15.72 ng. Several typical food packages were demonstrated with satisfactory recovery rates (87.5-110%) and precision (RSD ≤11.36%). These results suggested that the consumer plastic food containers are a significant source of direct exposure to nanoplastics in humans from the environment.

Predictive modeling of co-infection in lupus nephritis using multiple machine learning algorithms.

This study aimed to analyze peripheral blood lymphocyte subsets in lupus nephritis (LN) patients and use machine learning (ML) methods to establish an effective algorithm for predicting co-infection in LN. This study included 111 non-infected LN patients, 72 infected LN patients, and 206 healthy controls (HCs). Patient information, infection characteristics, medication, and laboratory indexes were recorded. Eight ML methods were compared to establish a model through a training group and verify the results in a test group. We trained the ML models, including Logistic Regression, Decision Tree, K-Nearest Neighbors, Support Vector Machine, Multi-Layer Perceptron, Random Forest, Ada boost, Extreme Gradient Boosting (XGB), and further evaluated potential predictors of infection. Infected LN patients had significantly decreased levels of T, B, helper T, suppressor T, and natural killer cells compared to non-infected LN patients and HCs. The number of regulatory T cells (Tregs) in LN patients was significantly lower than in HCs, with infected patients having the lowest Tregs count. Among the ML algorithms, XGB demonstrated the highest accuracy and precision for predicting LN infections. The innate and adaptive immune systems are disrupted in LN patients, and monitoring lymphocyte subsets can help prevent and treat infections. The XGB algorithm was recommended for predicting co-infection in LN.

Vertical migration behavior simulation and prediction of Pb and Cd in co-contaminated soil around Pb-Zn smelting slag site.

Heavy metal migration in soil poses a serious threat to the soil and groundwater. Understanding the migration pattern of heavy metals (HMs) under different factors could provide a more reasonable position for pollution evaluation and targetoriented treatment of soil heavy metal. In this study, the migration behavior of Pb and Cd in co-contaminated soil under different pH and ionic strength (NaCl concentration) was simulated using convective dispersion equation (CDE). We predicted the migration trends of Pb and Cd in soils after 5, 10, and 20 years via PHREEQC. The results showed that the migration time of Cd in the soil column experiment was about 60 days faster than that of Pb, and the migration trend was much steeper. The CDE was proved to describe the migration behavior of Pb and Cd (R2 > 0.75) in soil. The predicted results showed that Cd migrated to 15-20 cm of soil within 7 years and Pb stayed mainly in the top 0-6 cm of soil within 5 years as the duration of irrigation increased. Overall, our study is expected to provide new insight into the migration of heavy metal in soil ecosystems and guidance for reducing risk of heavy metal in the environment.

Transcription factor BACH1 in cancer: roles, mechanisms, and prospects for targeted therapy.

Transcription factor BTB domain and CNC homology 1 (BACH1) belongs to the Cap 'n' Collar and basic region Leucine Zipper (CNC-bZIP) family. BACH1 is widely expressed in mammalian tissues, where it regulates epigenetic modifications, heme homeostasis, and oxidative stress. Additionally, it is involved in immune system development. More importantly, BACH1 is highly expressed in and plays a key role in numerous malignant tumors, affecting cellular metabolism, tumor invasion and metastasis, proliferation, different cell death pathways, drug resistance, and the tumor microenvironment. However, few articles systematically summarized the roles of BACH1 in cancer. This review aims to highlight the research status of BACH1 in malignant tumor behaviors, and summarize its role in immune regulation in cancer. Moreover, this review focuses on the potential of BACH1 as a novel therapeutic target and prognostic biomarker. Notably, the mechanisms underlying the roles of BACH1 in ferroptosis, oxidative stress and tumor microenvironment remain to be explored. BACH1 has a dual impact on cancer, which affects the accuracy and efficiency of targeted drug delivery. Finally, the promising directions of future BACH1 research are prospected. A systematical and clear understanding of BACH1 would undoubtedly take us one step closer to facilitating its translation from basic research into the clinic.

SOX on tumors, a comfort or a constraint?

The sex-determining region Y (SRY)-related high-mobility group (HMG) box (SOX) family, composed of 20 transcription factors, is a conserved family with a highly homologous HMG domain. Due to their crucial role in determining cell fate, the dysregulation of SOX family members is closely associated with tumorigenesis, including tumor invasion, metastasis, proliferation, apoptosis, epithelial-mesenchymal transition, stemness and drug resistance. Despite considerable research to investigate the mechanisms and functions of the SOX family, confusion remains regarding aspects such as the role of the SOX family in tumor immune microenvironment (TIME) and contradictory impacts the SOX family exerts on tumors. This review summarizes the physiological function of the SOX family and their multiple roles in tumors, with a focus on the relationship between the SOX family and TIME, aiming to propose their potential role in cancer and promising methods for treatment.

SOX12 Facilitates Hepatocellular Carcinoma Progression and Metastasis through Promoting Regulatory T-Cells Infiltration and Immunosuppression.

Despite the success of immunotherapy in treating hepatocellular carcinoma (HCC), HCC remains a severe threat to health. Here, a crucial transcription factor, SOX12, is revealed that induces the immunosuppression of liver tumor microenvironment. Overexpressing SOX12 in HCC syngeneic models increases intratumoral regulatory T-cell (Treg) infiltration, decreases CD8+T-cell infiltration, and hastens HCC metastasis. Hepatocyte-specific SOX12 knockout attenuates DEN/CCl4-induced HCC progression and metastasis, whereas hepatocyte-specific SOX12 knock-in accelerates these effects. Mechanistically, SOX12 transcriptionally activates C-C motif chemokine ligand 22 (CCL22) expression to promote the recruitment and suppressive activity of Tregs. Moreover, SOX12 transcriptionally upregulates CD274 expression to suppress CD8+T-cell infiltration. Either knockdown of CCL22 or PD-L1 dampens SOX12-mediated HCC metastasis. Blocking of CC chemokine receptor 4 (CCR4), a receptor for CCL22, by inhibitor C-021 or Treg-specific knockout of CCR4 inhibits SOX12-mediated HCC metastasis. Transforming growth factor-ß1 (TGF-ß1)/TGFßR1-Smad2/3/4 is identified as a key upstream signaling for SOX12 overexpression in HCC cells. Combining C-021 or TGFßR1 inhibitor galunisertib with anti-PD-L1 exhibits an enhanced antitumor effect in two HCC models. Collectively, the findings demonstrate that SOX12 contributes to HCC immunosuppression through the CCL22/CCR4-Treg and PD-L1-CD8+T axes. Blocking of CCR4 or TGFßR1 improves the efficacy of anti-PD-L1 in SOX12-mediated HCC.