New molecular mechanism of nanoplastics affecting cadmium protein toxicity: Conformational response and differential binding of human serum albumin.

The significant health risks of nanoplastics (NPs) and cadmium (Cd) are currently attracting a great deal of attention and research. At present, the effects and mechanisms of NPs and Cd on human serum albumin (HSA), a key functional protein in the organism on transportation, remain unknown. Here, the differences in the effects and mechanisms of action of Cd alone and composite systems (NPsCd) were explored by enzyme activity assay, multi-spectroscopy analysis and molecular docking. The results showed that HSA activity was inhibited and decreased to 80 % and 69.55 % (Cd = 30 mg/L) by Cd alone and NPs-Cd exposure, respectively. Exposure to Cd induced backbone disruption and protein defolding of HSA, and secondary structure disruption was manifested by the reduction of α-helix. Cd exposure also induces fluorescence sensitization of HSA. Notably, the addition of NPs further exacerbated the effects associated with Cd exposure, which was consistent with the changes in HSA activity. Thus, the above conformational changes may be responsible for inducing the loss of enzyme activity. Moreover, it was determined by RLS spectroscopy that NPs-Cd bound to HSA in the form of protein crowns. Molecular docking has further shown that Cd binds to the surface of Sudlow site II of HSA, suggesting that Cd impairs the function of HSA by affecting the protein structure. More importantly, the addition of NPs further exacerbated the disruption of the protein structure by the adherent binding of HSA on the surface of the plastic particles, which induced a greater change in the enzyme activity. This study provides useful perspectives for investigating the impact of composite pollution on HSA of human functional proteins.

Prognostic value analysis and survival model construction of different treatment methods for advanced intestinal type gastric adenocarcinoma.

Background: Intestinal-type gastric adenocarcinoma, representing 95 % of gastric malignancies, originates from the malignant transformation of gastric gland cells. Despite its prevalence, existing methods for prognosis evaluation of this cancer subtype are inadequate. This study aims to enhance patient-specific prognosis evaluation by analyzing the clinicopathological characteristics and prognostic risk factors of intestinal-type gastric adenocarcinoma patients using data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (NCI). Methods: We extracted clinical data for patients diagnosed with intestinal-type gastric adenocarcinoma between 2010 and 2015 from the SEER database, selecting 257 cases based on predefined inclusion and exclusion criteria. Independent risk factors for overall survival (OS) and cancer-specific survival (CSS) were identified using a Cox regression model. A nomogram model for predicting OS or CSS was developed from the Cox risk regression analysis and validated through the consistency index (C-index), ROC curve, and calibration curve. Results: Age, primary tumor resection, chemotherapy, lymph node metastasis, and tumor size were identified as independent prognostic factors for OS and CSS (P < 0.05). The nomogram model, constructed from these indicators, demonstrated superior predictive consistency for OS and CSS compared to the AJCC-TNM staging system. ROC curve analysis confirmed the model's higher accuracy, and calibration curve analysis indicated good agreement between the nomogram's predictions and actual observed outcomes. Conclusion: The nomogram model derived from SEER database analyses accurately predicts OS and CSS for patients with intestinal-type gastric adenocarcinoma. This model promises to facilitate more tailored treatments in clinical practice.

ptx3a+ fibroblast/epicardial cells provide a transient macrophage niche to promote heart regeneration.

Macrophages conduct critical roles in heart repair, but the niche required to nurture and anchor them is poorly studied. Here, we investigated the macrophage niche in the regenerating heart. We analyzed cell-cell interactions through published single-cell RNA sequencing datasets and identified a strong interaction between fibroblast/epicardial (Fb/Epi) cells and macrophages. We further visualized the association of macrophages with Fb/Epi cells and the blockage of macrophage response without Fb/Epi cells in the regenerating zebrafish heart. Moreover, we found that ptx3a+ epicardial cells associate with reparative macrophages, and their depletion resulted in fewer reparative macrophages. Further, we identified csf1a expression in ptx3a+ cells and determined that pharmacological inhibition of the csf1a pathway or csf1a knockout blocked the reparative macrophage response. Moreover, we found that genetic overexpression of csf1a enhanced the reparative macrophage response with or without heart injury. Altogether, our studies illuminate a cardiac Fb/Epi niche, which mediates a beneficial macrophage response after heart injury.

Microscopic and spectroscopic analysis of atmospheric iron-containing single particles in Lhasa, Tibet.

The Tibetan Plateau, known as the "Third Pole", is currently in a state of perturbation caused by intensified human activity. In this study, 56 samples were obtained at the five sampling sites in typical area of Lhasa city and their physical and chemical properties were investigated by TEM/EDS, STXM, and NEXAFS spectroscopy. After careful examination of 3387 single particles, the results showed that Fe should be one of the most frequent metal elements. The Fe-containing single particles in irregular shape and micrometer size was about 7.8% and might be mainly from local sources. Meanwhile, the Fe was located on the subsurface of single particles and might be existed in the form of iron oxide. Interestingly, the core-shell structure of iron-containing particles were about 38.8% and might be present as single-, dual- or triple-core shell structure and multi-core shell structure with the Fe/Si ratios of 17.5, 10.5, 2.9 and 1.2, respectively. Meanwhile, iron and manganese were found to coexist with identical distributions in the single particles, which might induce a synergistic effect between iron and manganese in catalytic oxidation. Finally, the solid spherical structure of Fe-containing particles without an external layer were about 53.4%. The elements of Fe and Mn were co-existed, and might be presented as iron oxide-manganese oxide-silica composite. Moreover, the ferrous and ferric forms of iron might be co-existed. Such information can be valuable in expanding our understanding of Fe-containing particles in the Tibetan Plateau atmosphere.

Current Status of Novel Multifunctional Targeted Pt(IV) Compounds and Their Reductive Release Properties.

Platinum-based drugs are widely used in chemotherapy for various types of cancer and are considered crucial. Tetravalent platinum (Pt(IV)) compounds have gained significant attention and have been extensively researched among these drugs. Traditionally, Pt(IV) compounds are reduced to divalent platinum (Pt(II)) after entering cells, causing DNA lesions and exhibiting their anti-tumor effect. However, the available evidence indicates that some Pt(IV) derivatives may differ from the traditional mechanism and exert their anti-tumor effect through their overall structure. This review primarily focuses on the existing literature regarding targeted Pt(II) and Pt(IV) compounds, with a specific emphasis on their in vivo mode of action and the properties of reduction release in multifunctional Pt(IV) compounds. This review provides a comprehensive summary of the design and synthesis strategies employed for Pt(II) derivatives that selectively target various enzymes (glucose receptor, folate, telomerase, etc.) or substances (mitochondria, oleic acid, etc.). Furthermore, it thoroughly examines and summarizes the rational design, anti-tumor mechanism of action, and reductive release capacity of novel multifunctional Pt(IV) compounds, such as those targeting p53-MDM2, COX-2, lipid metabolism, dual drugs, and drug delivery systems. Finally, this review aims to provide theoretical support for the rational design and development of new targeted Pt(IV) compounds.

Perioperative complication incidence and risk factors for retroperitoneal neuroblastoma in children: analysis of 571 patients.

BACKGROUND: Surgery plays an important role in the treatment of neuroblastoma. Perioperative complications may impact the course of neuroblastoma treatment. To date, comprehensive analyses of complications and risk factors have been lacking. METHODS: Patients with retroperitoneal neuroblastoma undergoing tumor resection were retrospectively analyzed between 2014 and 2021. The data collected included clinical characteristics, operative details, operative complications and postoperative outcomes. Risk factors for perioperative complications of retroperitoneal neuroblastoma were analyzed. RESULTS: A total of 571 patients were enrolled in this study. Perioperative complications were observed in 255 (44.7%) patients. Lymphatic leakage (28.4%), diarrhea (13.5%), and injury (vascular, nerve and organ; 7.5%) were the most frequent complications. There were three operation-related deaths (0.53%): massive hemorrhage (n = 1), biliary tract perforation (n = 1) and intestinal necrosis (n = 1). The presence of image-defined risk factors (IDRFs) [odds ratio (OR) = 2.09, P < 0.01], high stage of the International Neuroblastoma Risk Group staging system (INRGSS) (OR = 0.454, P = 0.04), retroperitoneal lymph node metastasis (OR = 2.433, P = 0.026), superior mesenteric artery encasement (OR = 3.346, P = 0.003), and inferior mesenteric artery encasement (OR = 2.218, P = 0.019) were identified as independent risk factors for perioperative complications. CONCLUSIONS: Despite the high incidence of perioperative complications, the associated mortality rate was quite low. Perioperative complications of retroperitoneal neuroblastoma were associated with IDRFs, INRGSS, retroperitoneal lymph node metastasis and vascular encasement. Patients with high-risk factors should receive more serious attention during surgery but should not discourage the determination to pursue total resection of neuroblastoma. Video Abstract (MP4 94289 KB).

Efficient degradation of formaldehyde based on DFT-screened metal-doped C3N6 monolayer photocatalysts: performance evaluation and mechanistic insights.

Photocatalytic oxidation is an efficient and promising technology for reducing indoor pollution levels of formaldehyde (HCHO). However, developing efficient and low-cost photocatalysts for the removal of HCHO remains challenging due to the time-consuming and expensive nature of traditional "trial and error" and "directed research" approaches. To achieve this goal, first-principles density functional theory (DFT) calculations were conducted to high-throughput screen candidate TM-C3N6 photocatalysts for high-performance degradation of HCHO. The results revealed that Zr-C3N6 and Hf-C3N6 in functionalizing C3N6 with 28 transition metals showed excellent adsorption energy of HCHO, boosting the highly effective capture of HCHO. Meanwhile, an excellent adsorption performance mechanism was further elicited by the electric structure-property relationship. In addition, reaction mechanisms for HCHO degradation and three potential reaction pathways for HCHO degradation were systematically evaluated. Our findings indicated that hydroxyl-assisted dehydrogenation and oxygen-assisted dehydrogenation are the most favorable pathways, with rate-limiting steps involving the formation of ˙OH and ˙O radicals. Overall, this study may provide new insights into a high-throughput screening of novel photocatalysts that are both high-performing and low-cost for the removal of formaldehyde. This, in turn, can accelerate the experimental development process and reduce the associated costs and time consumption.

Bioinformatical analysis of the key differentially expressed genes for screening potential biomarkers in Wilms tumor.

Wilms tumor (WT) is the most common pediatric renal malignant tumor in the world. Overall, the prognosis of Wilms tumor is very good. However, the prognosis of patients with anaplastic tumor histology or disease relapse is still poor, and their recurrence rate, metastasis rate and mortality are significantly increased compared with others. Currently, the combination of histopathological examination and molecular biology is essential to predict prognosis and guide the treatment. However, the molecular mechanism has not been well studied. Genetic profiling may be helpful in some way. Hence, we sought to identify novel promising biomarkers of WT by integrating bioinformatics analysis and to identify genes associated with the pathogenesis of WT. In the presented study, the NCBI Gene Expression Omnibus was used to download two datasets of gene expression profiles related to WT patients for the purpose of detecting overlapped differentially expressed genes (DEGs). The DEGs were then uploaded to DAVID database for enrichment analysis. In addition, the functional interactions between proteins were evaluated by simulating the protein-protein interaction (PPI) network of DEGs. The impact of selected hub genes on survival in WT patients was analyzed by using the online tool R2: Genomics Analysis and Visualization Platform. The correlation between gene expression and the degree of immune infiltration was assessed by the Estimation of Stromal and Immune cells in Malignant Tumor tissues using the Expression (ESTIMATE) algorithm and the single sample GSEA. Top 12 genes were identified for further study after constructing a PPI network and screening hub gene modules. Kinesin family member 2C (KIF2C) was identified as the most significant gene predicting the overall survival of WT patients. The expression of KIF2C in WT was further verified by quantitative real-time polymerase chain reaction and immunohistochemistry. Furthermore, we found that KIF2C was significantly correlated with immune cell infiltration in WT. Our present study demonstrated that altered expression of KIF2C may be involved in WT and serve as a potential prognostic biomarker for WT patients.

Rapid detection of telomerase expression of neuroblastoma in paraffin-embedded tissue: combination of in situ hybridisation and quantitative PCR.

Neuroblastoma is a heterogeneous paediatric malignant tumour. Telomere maintenance mechanism (TMM) by telomerase activation or alternative lengthening of telomeres (ALT) is a hallmark of high-risk neuroblastoma. However, the prior assays for telomerase, such as TERT expression by RNA sequencing or microarrays, may not be easy to perform in many histopathology laboratories in hospitals. The aims of this study are to assess the utility of ultrasensitive single-cell RNA in situ hybridisation (RNAscope), immunohistochemistry, and RT-qPCR on formalin-fixed, paraffin-embedded tumour samples as diagnostic tools for detecting TERT expression in neuroblastoma. In this study, we detected MYCN amplification in 22 of 222 cases (10%), TERT rearrangements in 18 of 220 cases (8%), and ALT activation in 39 of 222 cases (18%) using fluorescence in situ hybridisation (FISH). By RNA in situ hybridisation, 36 of 210 (17%) pretreatment neuroblastomas were found to have TERT overexpression, which was significantly associated with the high-risk group (33/78, 42%), TERT rearrangements (16/18, 89%), and MYCN amplification (13/22, 59%). None of the tumours with ALT showed TERT staining. In our study, 19 of the 55 MYCN non-amplified high-risk neuroblastomas displayed TERT mRNA expression, including 13 of the 14 TERT rearrangements, none of the 30 ALT-positive cases, and a significant proportion (6/11, 55%) that did not have the aforementioned genomic anomalies. RT-qPCR results correlated well with RNAscope levels (Spearman's rho=0.621, p<0.001, n=94). In conclusion, TERT RNA in situ hybridisation and RT-qPCR are suitable methods to evaluate TERT expression in neuroblastoma. The combination of detection of the genomic alterations and TERT mRNA expression is a powerful strategy for TMM activation detection, which can categorise neuroblastomas into multiple clinical subgroups for risk stratification in routine histopathology practice.

AKT inhibitor Hu7691 induces differentiation of neuroblastoma cells.

While neuroblastoma accounts for 15% of childhood tumor-related deaths, treatments against neuroblastoma remain scarce and mainly consist of cytotoxic chemotherapeutic drugs. Currently, maintenance therapy of differentiation induction is the standard of care for neuroblastoma patients in clinical, especially high-risk patients. However, differentiation therapy is not used as a first-line treatment for neuroblastoma due to low efficacy, unclear mechanism, and few drug options. Through compound library screening, we accidently found the potential differentiation-inducing effect of AKT inhibitor Hu7691. The protein kinase B (AKT) pathway is an important signaling pathway for regulating tumorigenesis and neural differentiation, yet the relation between the AKT pathway and neuroblastoma differentiation remains unclear. Here, we reveal the anti-proliferation and neurogenesis effect of Hu7691 on multiple neuroblastoma cell lines. Further evidence including neurites outgrowth, cell cycle arrest, and differentiation mRNA marker clarified the differentiation-inducing effect of Hu7691. Meanwhile, with the introduction of other AKT inhibitors, it is now clear that multiple AKT inhibitors can induce neuroblastoma differentiation. Furthermore, silencing AKT was found to have the effect of inducing neuroblastoma differentiation. Finally, confirmation of the therapeutic effects of Hu7691 is dependent on inducing differentiation in vivo, suggesting that Hu7691 is a potential molecule against neuroblastoma. Through this study, we not only define the key role of AKT in the progression of neuroblastoma differentiation but also provide potential drugs and key targets for the application of differentiation therapies for neuroblastoma clinically.

Case report: Primary alveolar soft-part sarcoma of the lung in a child.

Alveolar soft-part sarcoma involving the lung is mostly metastatic in nature, while primary alveolar soft-part sarcoma involving the lung occurs more rarely. Herein, we report a rare case of a patient with primary alveolar soft-part sarcoma of the lung, which may represent the earliest onset of this condition reported thus far. In this patient, surgery was performed to excise the lesion to the greatest extent possible, and the combination of surgery with chemoradiotherapy and an antiangiogenic agent may provide an important reference for the development of standard or first-line treatment for such pediatric patients.

Roles of lncRNAs in childhood cancer: Current landscape and future perspectives.

According to World Health Organization (WHO), cancer is the leading cause of death for children and adolescents. Leukemias, brain cancers, lymphomas and solid tumors, such as neuroblastoma, ostesarcoma and Wilms tumors are the most common types of childhood cancers. Approximately 400,000 children and adolescents between the ages of 0 and 19 are diagnosed with cancer each year worldwide. The cancer incidence rates have been rising for the past few decades. Generally, the prognosis of childhood cancers is favorable, but the survival rate for many unresectable or recurring cancers is substantially worse. Although random genetic mutations, persistent infections, and environmental factors may serve as contributing factors for many pediatric malignancies, the underlying mechanisms are yet unknown. Long non-coding RNAs (lncRNAs) are a group of transcripts with longer than 200 nucleotides that lack the coding capacity. However, increasing evidence indicates that lncRNAs play vital regulatory roles in cancer initiation and development in both adults and children. In particular, many lncRNAs are stable in cancer patients' body fluids such as blood and urine, suggesting that they could be used as novel biomarkers. In support of this notion, lncRNAs have been identified in liquid biopsy samples from pediatric cancer patients. In this review, we look at the regulatory functions and underlying processes of lncRNAs in the initiation and progression of children cancer and discuss the potential of lncRNAs as biomarkers for early detection. We hope that this article will help researchers explore lncRNA functions and clinical applications in pediatric cancers.

Integrated Omics Approach to Discover Differences in the Metabolism of a New Tibetan Desmodesmus sp. in Two Types of Sewage Treatments.

Microalgae are now widely applied in municipal (YH_3) and industrial sewage (YH_4) treatments. Through integrated omics analysis, we studied the similarities and differences at the molecular level between the two different types of sewage treatment processes. The most significantly enriched gene ontology (GO) terms in both types of sewage treatments were the ribosome, photosynthesis, and proteasome pathways. The results show that the pathways of differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) were enriched for photosynthesis, glyoxylate and dicarboxylate metabolism, and carbon fixation in photosynthetic organisms. Considering YH_3 vs. YH_4, the metabolism of citrate, sedoheptulose-7P, and succinate was significantly upregulated. In addition, the results showed that the pathways of DEGs and DAMs were enriched in terms of amino acid metabolism and carotenoid biosynthesis in YH_4 vs. YH_3. The metabolism of S-Adenosyl-L-homocysteine was significantly downregulated, 2-oxobutanoate was significantly upregulated and downregulated, and the metabolism of abscisic acid glucose ester (ABA-GE) was also significantly upregulated. Overall, the results of this paper will help to improve the basic knowledge of the molecular response of microalgae to sewage treatments, and help design a response strategy based on microalgae for complex, mixed sewage treatments.

A new Desmodesmus sp. from the Tibetan Yamdrok Lake.

Revegetation of exposed sub-soil, while a desirable recovery strategy, often fails due to extreme soil chemical properties, such as low organic matter and pH levels. Microalgae play a key role in maintaining water quality in the lakes and rivers on the Qinghai-Tibet plateau. Plateau microalgae have extensive application prospects in environmental purification, biotechnology, medicine and cosmetics, food industry, and renewable energy. To identify the high biomass of microalgae present in nature, microalgae with the greatest biomass were screened from natural water samples through filtration, pre-culture, and plate scribing separation. Following identification via 18S rRNA sequencing as for the Desmodesmus sp., we constructed a neighbor-joining phylogenetic tree. The novel Desmodesmus sp. from the Tibetan Yamdrok Lake were identified through polyphasic taxonomy. Simultaneously, the sequence of the experimental samples and the target species were shown different following the identification and analysis of SNP and InDel loci. The light-absorbing properties of plateau Desmodesmus sp. have been investigated previously. The characteristic absorption peak of Desmodesmus sp. on the plateau was measured at 689 nm in the visible spectrum using full wavelength scanning with a UV-Vis spectrophotometer. For Desmodesmus sp. which is prone to settling in the process of amplification culture. By monitoring the change trend of total nitrogen, total phosphorus, pH and electrical conductivity in algae solution system, we determined that the logarithmic growth phase and the best transfer window of Desmodesmus sp. were at 15-20 days. This study can provide basic research methods for the study of microalgae in high altitude areas, and lay a foundation for the later study and application of microalgae.

Prognostic factors of pediatric pelvic and genitourinary rhabdomyosarcoma: An analysis based on SEER database.

Background: Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcomas in children. This study aimed to investigate the prognostic factors of pelvic and genitourinary RMS in children and evaluate the survival outcomes of these children treated with or without radiation therapy (RT). Methods: The Surveillance, Epidemiology, and End Results Program (SEER) database was required for children with pelvic and genitourinary RMS. Overall survival (OS) and cancer-specific survival (CSS) were analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched analyses. Results: For the 262 patients analyzed, the most common biological subtypes were embryonic (n=209, 79.8%) and alveolar (n=29, 11.1%). Patients with alveolar RMS had the worst prognosis (P < 0.05). The testis (n=122, 46.6%) was the most common location, followed by the urinary bladder (n=57, 21.8%) and prostate (n=48, 18.3%). Uterus RMS had the highest survival rate, followed by testis, urinary bladder, and prostate RMS. Favorable prognostic factors were age at diagnosis < 15 years, non-alveolar histological subtype, early tumor stage (localized/regional), specific sites (uterus and testis), and treatment (cancer-directed surgery and chemotherapy) (P < 0.05). Propensity score-matched analyses comparing the cohorts of patients treated with or without RT demonstrated no significant differences in prognostic survival (OS: P=0.872, CSS: P=0.713). Conclusion: The nomogram constructed based on independent prognostic factors may accurately predict survival rates at 1 and 5 years. Surgery and adjuvant chemotherapy can be effective treatments, but RT fails to guarantee a survival benefit. Therefore, prospective trials evaluating RT for pediatric pelvic and genitourinary RMS are warranted.

Associated factors on physical activity among childhood cancer survivors in Mainland China: a qualitative exploration applied health belief model.

PURPOSE: Regular physical activity (PA) is essential for childhood cancer survivors (CCS), yet most CCS have difficulty participating in it. The level of PA participation among CCS in China is lower than those of western countries, leading to a worse long-term survival of CCS in China. Here, the study aims to explore the associated factors on the PA performance among CCS. METHODS: From September to December 2020, the study used purposive sampling to recruit 35 families (88.9%) as sampling units among two hospitals in Hangzhou City, China. The data collection conducted two designs on semi-structured interviews with different roles under family structure - children (n = 35) and parents (n = 35) - respectively. The design of predetermined questions relied on the health belief model (HBM) as a thematic framework. The qualitative analysis applied codebook thematic analysis and used the deductive approach to finalize the main findings. RESULTS: The study only presented preliminary conclusions from interviews with CCS, which resulted in four themes (changes in PA performance; perceptions on participating PA; cognitions of PA; impacts from others) with eight sub-themes. In particular, CCS replied diversity changes in PA, but most of them mentioned the inactive PA after diagnosis, especially the decline of moderate-to-vigorous PA (MVPA). As for the "perceptions of PA," almost all CCS had substantial perceived benefits about PA, specifically on their physical well-being. All children also expressed perceived barriers to PA, including the side effects of disease and treatment, fatigue, academic burden, changes in psychological status, and lack of companions. On the cognitions of PA, the CCS had limited realizations of regular PA and low self-efficacy on MVPA. Furthermore, CCS expressed their need for support from their parents, school teachers, and healthcare providers. But in reality, they recieved less support on PA from these important people. CONCLUSION: The changes in PA after illness among CCS are apparent and unavoidable because of the interaction impacts from internal factors (e.g., personal characters, cognization, perceptions of PA) and external factors (e.g., disease effects, interpersonal supports). The findings explained the main elements under HBM but also provided explored views as the evidence on developing theories and guiding motivations and practices on PA among CCS. IMPLICATIONS FOR CANCER SURVIVORS: In this exploratory study of 35 CCS, we identified the current situation of PA among CCS in China and explored the associated factors. As the first qualitative study on the CCS in mainland China, the study considered particular effects on social culture and living environment.

Neoadjuvant transcatheter arterial chemoembolization and systemic chemotherapy for the treatment of undifferentiated embryonal sarcoma of the liver in children.

BACKGROUND: Undifferentiated embryonal sarcoma of the liver (UESL) is a rare and aggressive mesenchymal tumor in children. Herein, we describe our experience in neoadjuvant therapy (NAT) and subsequent surgery for the treatment of UESL in children. AIM: To evaluate the efficacy of NAT and explore a new choice for successful operation of UESL in children. METHODS: We retrospectively analyzed six patients newly diagnosed with unresectable UESL who received NAT and then surgery at our center between January 2004 and December 2019. The tumor was considered unresectable if it involved a large part of both lobes of the liver or had invaded the main hepatic vessels or inferior vena cava. The NAT included preoperative transcatheter arterial chemoembolization (TACE) and systemic chemotherapy. The patients were 4 boys and 2 girls with a mean age of 7 years. The longest tumor at presentation ranged from 8.6 to 14.8 cm (mean, 12 cm). Extrahepatic metastases were present in 2 cases. Preoperative systemic chemotherapy was administered 3 wk after TACE. Tumor resection was performed 3 wk after one or two cycles of NAT. The patients received systemic chemotherapy after surgery. RESULTS: All patients successfully underwent NAT and complete resection. The tumor volumes decreased by 18.2%-68.7%, with a mean decrease of 36% after 1 cycle of NAT (t = 3.524, P = 0.017). According to the Response Evaluation Criteria In Solid Tumors criteria, 4 patients had a partial response and underwent surgery, while 2 had stable disease and received another cycle of NAT before surgery. Massive tumor necrosis was seen on pathological examination of the surgical specimen: > 90% necrosis in two, > 50% necrosis in three, and 25% necrosis in 1, with an average of 71.8%. Post-NAT complications included fever, nausea and vomiting, and mild bone marrow suppression. Elevated alanine transaminase levels occurred in all patients, which returned to normal within 7-10 d after treatment. No cardiac or renal toxicity, severe hepatic dysfunction, bleeding and non-target embolization were observed in the patients. The median follow-up period was 8 years with an overall survival of 100%. CONCLUSION: NAT effectively reduced tumor volume, cleared the tumor margin, and caused massive tumor necrosis. This may be a promising choice for successful surgery of UESL in children.

Ferric ions release from iron-binding protein: Interaction between acrylamide and human serum transferrin and the underlying mechanisms of their binding.

Acrylamide (ACR) is a surprisingly common chemical due to its widespread use in industry and various other applications. However, its toxicity is a matter of grave concern for public health. Even worse, ACR is frequently detected in numerous fried or baked carbohydrate-rich foods due to the Maillard browning reaction. Herein, this study intends to delineate the underlying molecular mechanisms of Fe ions released from iron-binding protein transferrin (TF) after acrylamide binding by combining multiple methods, including multiple complementary spectroscopic techniques (UV-Vis, fluorescence, and circular dichroism spectroscopy), isothermal titration calorimetry, ICP-MS measurements, and modeling simulations. Results indicated that free Fe was released from TF only under high-dose ACR exposure (>100 µM). Acrylamide binding induced the loosening and unfolding of the backbone and polypeptide chain and destroyed the secondary structure of TF, thereby leading to protein misfolding and denaturation of TF and forming a larger size of TF agglomerates. Of which, H-binding and van der Waals force are the primary driving force during the binding interaction between ACR and TF. Further modeling simulations illustrated that ACR prefers to bind to the hinge region connecting the C-lobe and N-lobe, after that it attaches to the Fe binding sites of this protein, which is the cause of free Fe release from TF. Moreover, ACR interacted with the critical fluorophore residues (Tyr, Trp, and Phe) in the binding pocket, which might explain such a phenomenon of fluorescence sensitization. The two binding sites (Site 2 and Site 3) located around the Fe (III) ions with low-energy conformations are more suitable for ACR binding. Collectively, our study demonstrated that the loss of iron in TF caused by acrylamide-induced structural and conformational changes of transferrin.

Comparison of Widely Targeted Metabolomics and Untargeted Metabolomics of Wild Ophiocordyceps sinensis.

The authors of this paper conducted a comparative metabolomic analysis of Ophiocordyceps sinensis (OS), providing the metabolic profiles of the stroma (OSBSz) and sclerotia (OSBSh) of OS by widely targeted metabolomics and untargeted metabolomics. The results showed that 778 and 1449 metabolites were identified by the widely targeted metabolomics and untargeted metabolomics approaches, respectively. The metabolites in OSBSz and OSBSh are significantly differentiated; 71 and 96 differentially expressed metabolites were identified by the widely targeted metabolomics and untargeted metabolomics approaches, respectively. This suggests that these 71 metabolites (riboflavine, tripdiolide, bromocriptine, lumichrome, tetrahymanol, citrostadienol, etc.) and 96 metabolites (sancycline, vignatic acid B, pirbuterol, rubrophen, epalrestat, etc.) are potential biomarkers. 4-Hydroxybenzaldehyde, arginine, and lumichrome were common differentially expressed metabolites. Using the widely targeted metabolomics approach, the key pathways identified that are involved in creating the differentiation between OSBSz and OSBSh may be nicotinate and nicotinamide metabolism, thiamine metabolism, riboflavin metabolism, glycine, serine, and threonine metabolism, and arginine biosynthesis. The differentially expressed metabolites identified using the untargeted metabolomics approach were mainly involved in arginine biosynthesis, terpenoid backbone biosynthesis, porphyrin and chlorophyll metabolism, and cysteine and methionine metabolism. The purpose of this research was to provide support for the assessment of the differences between the stroma and sclerotia, to furnish a material basis for the evaluation of the physical effects of OS, and to provide a reference for the selection of detection methods for the metabolomics of OS.