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Acesulfame potassium (ACK) was generally regarded as innocuous and extensively ingested. Nevertheless, ACK has recently gained attention as a burgeoning pollutant that has the potential to induce a range of health hazards, particularly to the digestive system. Herein, we uncover that ACK initiates inflammatory bowel disease (IBD) in mice and zebrafish, as indicated by the aggregation of macrophages in the intestine and the inhibition of intestinal mucus secretion. Transcriptome analysis of mice and zebrafish guts revealed that exposure to ACK typically impacts the cell cycle, focal adhesion, and PI3K-Akt signaling pathways. Using pharmacological approaches, we demonstrate that the PI3K-Akt signaling pathway and the generation of reactive oxygen species (ROS) triggered by cell division are not significant factors in the initiation of IBD caused by ACK. Remarkably, inhibition of the focal adhesion pathway is responsible for the IBD onset induced by ACK. Our results indicate the detrimental impacts and possible underlying mechanisms of ACK on the gastrointestinal system and provide insights for making informed choices about everyday dietary habits., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Clinical treatment of diabetic refractory ulcers is impeded by chronic inflammation and cell dysfunction associated with wound healing. The significant clinical application of bFGF in wound healing is limited by its instability in vivo . Sulfur has been applied for the treatment of skin diseases in the clinic for antibiosis. We previously found that sulfur incorporation improves the ability of selenium nanoparticles to accelerate wound healing, yet the toxicity of selenium still poses a risk for its clinical application. To obtain materials with high pro-regeneration activity and low toxicity, we explored the mechanism by which selenium-sulfur nanoparticles aid in wound healing via RNA-Seq and designed a nanoparticle called Nano-S@bFGF, which was constructed from sulfur and bFGF. As expected, Nano-S@bFGF not only regenerated zebrafish tail fins and promoted skin wound healing but also promoted skin repair in diabetic mice with a profitable safety profile. Mechanistically, Nano-S@bFGF successfully coactivated the FGFR and Hippo signalling pathways to regulate wound healing. Briefly, the Nano-S@bFGF reported here provides an efficient and feasible method for the synthesis of bioactive nanosulfur and bFGF. In the long term, our results reinvigorated efforts to discover more peculiar unique biofunctions of sulfur and bFGF in a great variety of human diseases., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Xiaojia Chen reports financial support was provided by Jinan University. Xiaojia Chen reports a relationship with Jinan University that includes: non-financial support. Xiaojia Chen, An Hong, Jieqiong Cao, Yibo Zhang, Zijian Su has patent pending to Nano-S@bFGF. The remaining authors declare no potential conflict of interests. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, with a global prevalence of 25%. Patients with NAFLD are more likely to suffer from advanced liver disease, cardiovascular disease, or type II diabetes. However, unfortunately, there is still a shortage of FDA-approved therapeutic agents for NAFLD. Lian-Mei-Yin (LMY) is a traditional Chinese medicine formula used for decades to treat liver disorders. It has recently been applied to type II diabetes which is closely related to insulin resistance. Given that NAFLD is another disease involved in insulin resistance, we hypothesize that LMY might be a promising formula for NAFLD therapy. Herein, we verify that the LMY formula effectively reduces hepatic steatosis in diet-induced zebrafish and NAFLD model mice in a time- and dose-dependent manner. Mechanistically, LMY suppresses Yap1-mediated Foxm1 activation, which is crucial for the occurrence and development of NAFLD. Consequently, lipogenesis is ameliorated by LMY administration. In summary, the LMY formula alleviates diet-induced NAFLD in zebrafish and mice by inhibiting Yap1/Foxm1 signaling-mediated NAFLD pathology.

The process of smelting and purifying the catalyst precursor salt from minerals is extremely complex, which directly leads to high catalyst costs and serious secondary pollution. In order to achieve energy saving and emission reduction in the catalyst preparation process, in-situ synthesis of catalyst materials from natural minerals is a new research direction. In this study, we firstly explored the optimal X value of Mn X Fe 3-X O 4 for the NH 3 selective catalytic reduction of NO (NH 3 -SCR) reaction, i.e., the Mn, Fe ratio, and then prepared a novel highly active mineral-based pure phase Mn X Fe 3-X O 4 spinel NH 3 -SCR catalyst by natural ferromanganese ore fines with iron-red fines (Fe 2 O 3 ) allotment through in situ solid-phase synthesis and magnetic separation methods according to this ratio. The results show that the X value of 1.5 (Mn 1.5 Fe 1.5 O 4 ) is the best for NH 3 -SCR reaction. Mn 1.5 Fe 1.5 O 4 nano-particles (201 nm) has nearly 100 % NO conversion (with 5 % H 2 O (g) ) at 125-300 °C. The combination of characterizations and density functional theory (DFT) calculation shows that the catalytic process of Eley-Rideal (E-R) dehydrogenation is enhanced at both the active site Mn site and Fe site, which is a key factor in the acceleration of the NH 3 -SCR reaction with increasing X value at the Mn X Fe 3-X O 4 surface., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

NKD inhibitor of WNT signaling pathway 2 (NKD2) is an emerging player in cancer onset and progression. Here, it was confirmed that THCA patients have robustly expressed NKD2, which was linked to an advanced pathologic stage. The prognosis was worse for those with high NKD2 levels. Functionally, ectopically produced NKD2 promotes THCA cell proliferation, whereas NKD2 knockdown impairs the ability of THCA cells to proliferate. Mechanically, ectopically expressed NKD2 activated NF-κB transcriptional activity, whereas NKD2-deficient THCA cells showed lower NF-κB transcriptional activity. As a result, NKD2 activates the NF-κB signaling pathway, encouraging the growth of THCA cells., (© 2023. The Author(s).)

Umbilical cord blood (UCB) is an advantageous source for hematopoietic stem/progenitor cell (HSPC) transplantation, yet the current strategies for large-scale and cost-effective UCB-HSPC preparation are still unavailable. To overcome these obstacles, we systematically evaluate the feasibility of our newly identified CH02 peptide for ex vivo expansion of CD34 + UCB-HSPCs. We herein report that the CH02 peptide is specifically enriched in HSPC proliferation via activating the FLT3 signaling. Notably, the CH02-based cocktails are adequate for boosting 12-fold ex vivo expansion of UCB-HSPCs. Meanwhile, CH02-preconditioned UCB-HSPCs manifest preferable efficacy upon wound healing in diabetic mice via bidirectional orchestration of proinflammatory and anti-inflammatory factors. Together, our data indicate the advantages of the CH02-based strategy for ex vivo expansion of CD34 + UCB-HSPCs, which will provide new strategies for further development of large-scale HSPC preparation for clinical purposes.

Background: The overall prevalence of papillary thyroid carcinoma (PTC) patients is expanding along with an ongoing increase in thyroid cancer incidence. Patients with PTC who have lymph node metastases have a poor prognosis and a high death rate. There is an urgent need for indicators that can predict lymph node metastasis (LNM) before surgery as current imaging techniques, such as ultrasonography, do not have sufficient sensitivity to detect LNM. To predict independent risk factors for Central lymph node metastasis (CLNM) or Lateral lymph node metastasis (LLNM), we therefore developed two nomograms based on CLNM and LLNM, separately., Methods: In two centers, the Second Affiliated Hospital of Nanchang University and Yichun People's Hospital, we retrospectively analyzed clinicopathological characteristics of PTC patients. We utilized multivariate analysis to screen for variables that might be suspiciously related to CLNM or LLNM. Furthermore, we developed nomograms to graphically depict the independent risk valuables connected to lymph node metastasis in PTC patients., Result: Ultimately, 6068 PTC patients in all were included in the research. Six factors, including age<45, male, mETE, TSH>1.418, tumor size>4cm, and location (multicentric and lobe), were observed to be related to CLNM. Age<45, male, mETE (minimal extrathyroidal extension), multifocality, TSH≥2.910, CLNM positive, and tumor size>4cm were regarded as related risk factors for LLNM. The two nomograms developed subsequently proved to have good predictive power with 0.706 and 0.818 and demonstrated good clinical guidance functionality with clinical decision curves and impact curves., Conclusion: Based on the successful establishment of this dual-institution-based visual nomogram model, we found that some clinical features are highly correlated with cervical lymph node metastasis, including CLNM and LLNM, which will better help clinicians make individualized clinical decisions for more effectively rationalizing managing PTC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Zhang, Jiang, Peng, Xu, Shu, Su, Yi and Lv.)

The utilization of virulent chromium slag has always been a worldwide problem, and lots of C-bearing dust produced in steel industry has not been utilized efficiently. Sintering is a potential method to treat these two kinds of solid wastes, but it is limited by small treatment capacity, incomplete detoxification of Cr(Ⅵ) when they were directly added into sintering process. In this study, an innovative technology of co-processing chromium slag and C-bearing dust via composite agglomeration process (CAP)-blast furnace method was put forward and systematically investigated. In the CAP, the chromium slag and C-bearing dust were first made into composite pellets and added into the matrix feed for co-sintering. The results showed that, 20% chromium slag and 5% C-bearing dust could be co-disposed by the CAP without destroying the quality of the sinters. Cr(VI) was completely reduced to Cr(III) or metal Cr. 12.83% Cr existed as metal Cr, and the rest of Cr existed in spinel as (Mg, Fe)(Cr, Al) 2 O 4 or in silico-ferrite of calcium and alumina as Cr(Ⅲ). After blast furnace smelting, 90.22% Cr in sinters entered stainless mother liquor to be recycled., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Shark cartilage was created as a cancer-fighting diet because it was believed to have an element that may suppress tumor growth. Due to overfishing, sharks have become endangered recently, making it impossible to harvest natural components from shark cartilage for therapeutic development research. Previously, we identified a peptide SAIF from shark cartilage with an-tiangiogenic and anti-tumor effects, successfully expressed it in Escherichia coli by using genetic engineering techniques. However, we did not elucidate the specific target of SAIF and its antiangiogenic molecular mechanism, which hindered its further drug development. Therefore, in this work, the exact mechanism of action was studied using various techniques, including cellular and in vivo animal models, computer-aided simulation, molecular target capture, and transcriptome sequencing analysis. With VEGF-VEGFR2 interaction and preventing the activation of VEGFR2/ERK signaling pathways, SAIF was discovered to decrease angiogenesis and hence significantly limit tumor development. The findings further demonstrated SAIF's strong safety and pharmaceutically potential. The evidence showed that SAIF, which is expressed by, is a potent and safe angiogenesis inhibitor and might be developed as a candidate peptide drug for the treatment of solid tumors such as hepatocellular carcinoma and other conditions linked with angiogenic overgrowth., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers worldwide, but current treatment options remain limited and cause serious life-threatening side effects. Aberrant FGFR4 signaling has been validated as an oncogenic driver of HCC, and EZH2, the catalytic subunit of the PRC2 complex, is a potential factor that contributes to acquired drug resistance in many tumors, including HCC. However, the functional relationship between these two carcinogenic factors, especially their significance for HCC treatment, remains unclear. In this study, we systematically evaluated the feasibility of a combination therapy targeting FGFR4 and EZH2 for HCC., Methods: RNA sequencing data of patients with Liver hepatocellular carcinoma (LIHC) from The Cancer Genome Atlas (TCGA) were analyzed to determine FGFR4 and EZH2 expression and their interaction with prognosis. Moreover, the HCC cell lines, zebrafish/mouse HCC xenografts and zebrafish HCC primary tumors were treated with FGFR4 inhibitor (Roblitinib) and/or EZH2 inhibitor (CPI-169) and then subjected to cell proliferation, viability, apoptosis, and tumor growth analyses to evaluate the feasibility of combination therapy for HCC both in vitro and in vivo. Furthermore, RNA-Seq was performed in combination with ChIP-Seq data analysis to investigate the critical mechanism underlying the combination treatment with Roblitinib and CPI-169., Results: EZH2 accumulated through the non-canonical NF-kB signaling in response to FGFR4 inhibitor treatment, and the elevated EZH2 levels led to the antagonism of HCC against Roblitinib (FGFR4 inhibitor). Notably, knockdown of EZH2 sensitized HCC cells to Roblitinib, while the combination treatment of Roblitinib and CPI-169 (EZH2 inhibitor) synergistically induced the HCC cell apoptosis in vitro and suppressed the zebrafish/mouse HCC xenografts and zebrafish HCC primary tumors development in vivo. Moreover, Roblitinib and CPI-169 synergistically inhibited HCC development via repressing YAP signaling., Conclusions: Collectively, our study highlighted the potential of the therapeutic combination of FGFR4 and EZH2 inhibitors, which would provide new references for the further development of clinical treatment strategies for HCC., (© 2023. The Author(s).)

Liver fibrosis represents a significant health hazard with a high morbidity rate and an increased risk of liver cancer. Targeting overactivated Fibroblast growth factor receptor 2 (FGFR2) is a promising strategy to counteract collagen accumulation during liver fibrosis. However, there is a shortage of drugs to specifically block the activation of FGFR2 in liver fibrosis patients. Data mining, cell validation, and animal studies showed a positive correlation between FGFR2 overexpression and liver fibrosis development. Novel FGFR2 inhibitors were screened using a microarray-based high-throughput binding analysis. The effectiveness of each candidate was validated through simulated docking, binding affinity verification, single-point mutation validation, and in vitro kinase inhibition measurements to demonstrate the ability of each inhibitor to block the catalytic pocket and reverse FGFR2 overactivation. A specific FGFR2 inhibitor, cynaroside (CYN, also known as luteoloside), was screened based on the finding that FGFR2 promotes hepatic stellate cell (HSC) activation and collagen secretion in hepatocytes. The results from cellular assays showed that CYN can inhibit FGFR2 hyperactivation resulting from its overexpression and excessive basic fibroblast growth factor (bFGF), reducing HSC activation and collagen secretion in hepatocytes. Animal experiments on a carbon tetrachloride (CCl 4 ) mouse model and a nonalcoholic steatohepatitis mouse model indicate that CYN treatment reduces liver fibrosis during fibrosis formation. These findings suggest that CYN prevents liver fibrosis formation at the cell level and in mouse models.

Triclocarban (TCC) is a widely used environmental endocrine-disrupting chemical (EDC). Articular injury of EDCs has been reported; however, whether and how TCCs damage the joint have not yet been determined. Herein, we revealed that exposure to TCC caused osteoarthritis (OA) within the zebrafish anal fin. Mechanistically, TCC stimulates the expression of DNMT1 and initiates DNA hypermethylation of the type II collagen coding gene, which further suppresses the expression of type II collagen and other extracellular matrices. This further results in decreased cartilage tissue and narrowing of the intraarticular space, which is typical of the pathogenesis of OA. The regulation of OA occurrence by TCC is conserved between zebrafish cartilage tissue and human chondrocytes. Our findings clarified the hazard and potential mechanisms of TCC towards articular health and highlighted DNMT1 as a potential therapeutic target for OA caused by TCC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Globally, millions of patients suffer from regenerative deficiencies, such as refractory wound healing, which is characterized by excessive inflammation and abnormal angiogenesis. Growth factors and stem cells are currently employed to accelerate tissue repair and regeneration; however, they are complex and costly. Thus, the exploration of new regeneration accelerators is of considerable medical interest. This study developed a plain nanoparticle that accelerates tissue regeneration with the involvement of angiogenesis and inflammatory regulation., Methods: Grey selenium and sublimed sulphur were thermalized in PEG-200 and isothermally recrystallised to composite nanoparticles (Nano-Se@S). The tissue regeneration accelerating activities of Nano-Se@S were evaluated in mice, zebrafish, chick embryos, and human cells. Transcriptomic analysis was performed to investigate the potential mechanisms involved during tissue regeneration., Results: Through the cooperation of sulphur, which is inert to tissue regeneration, Nano-Se@S demonstrated improved tissue regeneration acceleration activity compared to Nano-Se. Transcriptome analysis revealed that Nano-Se@S improved biosynthesis and ROS scavenging but suppressed inflammation. The ROS scavenging and angiogenesis-promoting activities of Nano-Se@S were further confirmed in transgenic zebrafish and chick embryos. Interestingly, we found that Nano-Se@S recruits leukocytes to the wound surface at the early stage of regeneration, which contributes to sterilization during regeneration., Conclusion: Our study highlights Nano-Se@S as a tissue regeneration accelerator, and Nano-Se@S may provide new inspiration for therapeutics for regenerative-deficient diseases., (© 2023. The Author(s).)

Acne is a chronic skin condition that has serious consequences for mental and social well-being because it frequently occurs on the face. Several acne treatment approaches have commonly been used but have been hampered by side effects or weak activity. Thus, the investigation of the safety and efficacy of anti-acne compounds is of considerable medical importance. Herein, an endogenous peptide (P5) derived from fibroblast growth factors 2 (FGF2) was conjugated to the polysaccharide hyaluronic acid (HA) to generate the bioconjugate nanoparticle HA-P5, which suppresses fibroblast growth factor receptors (FGFRs) to significantly rehabilitate acne lesions and reduce sebum accumulation in vivo and in vitro. Moreover, our results show that HA-P5 inhibits both fibroblast growth factor receptor 2 (FGFR2) and androgen receptor (AR) signalling in SZ95 cells, reverses the acne-prone transcriptome, and decreases sebum secretion. Furthermore, the cosuppression mechanism revealed that HA-P5 blocks FGFR2 activation, as well as the YTH N6-methyladenosine RNA binding protein F3 (YTHDF3) downstream molecules, including an N6-methyladenosine (m6A) reader that facilitates AR translation. More importantly, a significant difference between HA-P5 and the commercial FGFR inhibitor AZD4547 is that HA-P5 does not trigger the overexpression of aldo-keto reductase family 1 member C3 (AKR1C3), which blocks acne treatment by catalyzing the synthesis of testosterone. Overall, we demonstrate that a polysaccharide-conjugated and naturally derived oligopeptide HA-P5 can alleviate acne and act as an optimal FGFR2 inhibitor and reveal that YTHDF3 plays a crucial role in signalling between FGFR2 and AR., (© 2023. The Author(s).)

E-waste is a valuable resource for the recovery of secondary metals. However, traditional methods only focused on the extraction of Cu and noble metals (Au, Ag, etc.), and significant tin (Sn) loss occurred during the smelting or the leached. In this paper, a novel chemical vapor transport (CVT) process was proposed to separate and recycle Sn from e-waste to prepare nano-SnO 2 . The effect of roasting parameters on Sn volatilization and characterization of nano-SnO 2 were investigated using thermodynamic analysis, XRD, SEM, TEM, etc. The results indicated that Sn volatilization of 92.8 % was obtained under optimal roasting parameters under CO-CO 2 -N 2 atmosphere. In addition, nano-SnO 2 with a crystallinity of 99.9 %, an average grain size of 24.8 nm and a specific surface area of 97.9 m 2 /g was synthesized successfully., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In this study, the manganese (Mn) was doped in the MnFe 2 O 4 crystal by the solid-phase synthesis method. Under the optimum conditions (pH = 3), the max removal rate and adsorption quantity of Cr(VI) on MnFe 2 O 4 adsorbent obtain under pH = 3 were 92.54% and 5.813 mg/g, respectively. The DFT calculation results indicated that the adsorption energy (E ads ) between HCrO 4 - and MnFe 2 O 4 is -215.2 KJ/mol. The Cr(VI) is mainly adsorbed on the Mn atoms via chemical bonds in the form of HCrO 4 - . The adsorption of Mn on the MnFe 2 O 4 surface belonged to chemisorption and conformed to the Pseudo-second-order equation. The mechanism investigation indicated that the Mn in MnFe 2 O 4 has an excellent enhancement effect on the Cr(VI) removal process. The roles of Mn in the Cr(VI) removal process included two parts, providing adsorbing sites and being reductant. Firstly, the Cr(VI) is adsorbed onto the MnFe 2 O 4 via chemisorption. The Mn in MnFe 2 O 4 can form ionic bonds with the O atoms of HCrO 4 - /CrO 4 2- , thus providing the firm adsorbing sites for the Cr(VI). Subsequently, the dissolved Mn(II) can reduce Cr(VI) to Cr(III). The disproportionation of oxidized Mn(III) produced Mn(II), causing Mn(II) to continue to participate in the Cr(VI) reduction. Finally, the reduced Cr(III) is deposited on the MnFe 2 O 4 surface in the form of Cr(OH) 3 colloids, which can be separated by magnetic separation.

To produce Na 2 SnO 3, which is widely used in the ceramics and electroplating industries, a novel process for the preparation of sodium stannate from cassiterite concentrates was developed successfully by the authors' group. It was found that sodium stannosilicate (Na 8 SnSi 6 O 18 ) was easily formed due to the main gangue of quartz in cassiterite concentrates, which was almost insoluble and decreased the quality of Na 2 SnO 3 . The formation and transitions of Na 8 SnSi 6 O 18 in the SnO 2 -SiO 2 -Na 2 CO 3 system roasted under a CO-CO 2 atmosphere were determined. The results indicated that the formation of Na 8 SnSi 6 O 18 could be divided into two steps: SnO 2 reacted with Na 2 CO 3 to form Na 2 SnO 3 , and then Na 2 SnO 3 was rapidly combined with SiO 2 and Na 2 CO 3 to form low melting point Na 8 SnSi 6 O 18 . In addition, Na 8 SnSi 6 O 18 can be decomposed into Na 2 SiO 3 and Na 2 SnO 3 by using excess Na 2 CO 3 .

A novel composite binder (humic acid modified bentonite, HAMB) and two other binders (bentonite and Modified humic acid, MHA) were used to explore the effects of binders on the properties of magnetite green pellets in this study. The results of green pellet properties and drying tests show that the low doses of a humic substance-based binder can achieve the same effect as high doses of bentonite binder. A humic substance-based binder could be a promising organic binder to replace bentonite. Meanwhile, the influence mechanism of adding different binders on the strength of green pellet was discussed, and the relationship between moisture content in the pellet and the compression strength of three binders was determined. A TG-DSC analysis found that the novel composite binder (HAMB) was not a simple mix of humic acid and bentonite, in which a humic substance could change the structure of bentonite and reduce the thermal stability of bentonite, causing the HAMB composite binder to have a high decomposition temperature.

Background: Circular RNAs (circRNAs) are a newly described class of non-coding RNAs that play essential roles in regulating gene expression. However, to date, few studies have examined the roles of circRNAs in papillary thyroid carcinoma (PTC). In this study, we analyzed the expression of circ&#95;0001658 in PTC as well as its functions and associated mechanisms of action in PTC cells., Methods: Real-time quantitative polymerase chain reaction was used to determine the expression of circ&#95;0001658, miR-671-5p, and integrin subunit alpha 2 (ITGA2), and western blotting was performed to determine the levels of ITGA2 and phosphatidylinositide 3-kinase/protein kinase B pathway-related proteins in PTC cell lines. Cell Counting Kit-8 and Transwell analyses were conducted to examine the effects of circ&#95;0001658 on PTC cell function following the knockdown of circ&#95;0001658 expression. In addition, the targeting of circ&#95;0001658 and ITGA2 by miR-671-5p was verified using dual-luciferase reporter assays., Results: We demonstrated that circ&#95;0001658 and ITGA2 were significantly up-regulated in PTC tissues and cell lines. Knockdown of circ&#95;0001658 inhibited the growth and metastatic potential of PTC cells. MiR-671-5p targeted both circ&#95;0001658 and ITGA2. Mechanistically, circ&#95;0001658 promoted PTC progression by sponging miR-671-5p, up-regulating ITGA2 expression, and activating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. In summary, circ&#95;0001658 is a carcinogenesis-associated circRNA that regulates PI3K/AKT signaling via the miR-671-5p/ITGA2 axis and plays a role in promoting the progression of PTC., Conclusions: Our findings provide a theoretical basis for further molecular biological studies on the treatment of PTC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-3650/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Background: The carcinogenesis and prognosis of hepatocellular carcinoma (HCC) involve complex molecular mechanisms, and ferroptosis is related to the development and therapeutic efficacy of HCC, but the specific mechanism and prognostic role of ferroptosis-related genes in HCC have not been elucidated. Methods: Differentially expressed gene analysis, Cox regression, and unsupervised consensus clustering were applied to identify crucial ferroptosis regulators and establish ferroptosis-related subtypes in HCC. Random forest analysis and survival analysis were adopted to confirm FTL as the hub prognostic and diagnostic ferroptosis regulator in HCC. Results: The ferroptosis-related subtypes based on the crucial prognostic ferroptosis regulators showed that patients in fescluster A had a higher survival probability ( p < 0.001) and better clinical characteristics than patients in fescluster B in the TCGA-LIHC cohort. Patients with a high tumor mutation burden (TMB) in fescluster B presented a significantly poorer prognosis. FTL was the core ferroptosis regulator, and its low expression revealed a significant survival advantage compared with its high expression ( p = 0.03). The expression and predictive value of FTL were both closely related to the clinical features ( p < 0.05). Expression of FTL accurately distinguished HCC from normal tissues in the TCGA-LIHC cohort, ICGC cohort, and GSE14520 dataset. In addition, higher infiltrating fractions of immune cells, such as activated CD8 + T cells and Gamma delta T cells, mainly enriched immune-related signaling pathways, including the IL2-STAT3 signaling pathway and interferon-gamma response signaling pathway, and higher expression of immune checkpoints, including PDCD1, CTLA4, TIGIT, and CD83, were presented in patients with high FTL expression ( p < 0.05). Patients with high FTL were more sensitive to some targeted drugs, such as cisplatin, dasatinib, and sorafenib, than those with low FTL ( p < 0.05). A nomogram based on FTL accurately predicted the prognosis of HCC. Further knockdown of FTL was determined to significantly inhibit cell proliferation and migration in HCC. Conclusion: Our study validated ferroptosis-related subtypes and FTL with effective prognostic value in HCC and was beneficial for identifying candidates suitable for targeted drug therapy and immunotherapy, thereby offering further insight into individual treatment strategies to improve disease outcomes in HCC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ke, Wang, Su, Lin and Wu.)

In malignancies, fibroblast growth factor receptors (FGFRs) signaling is reinforced through overexpression of fibroblast growth factors (FGFs) or their receptors. FGFR2 has been proposed as a target for cancer therapy, because both the expression and activation of FGFR2 are boosted in various malignant carcinomas. Although several chemicals have been designed against FGFR2, they did not exhibit enough specificity and might bring potential accumulated toxicity. In this study, we developed an epitope peptide (P5) and its cyclic derivative (DcP5) based on the structure of FGF2 to limit the activation of FGFR2. The anticancer activities of P5 and DcP5 were examined in vitro and in vivo. Our results demonstrated that P5 significantly inhibited the cell proliferation in FGFR2-dependent manner in DU145 cells and retarded tumor growth in DU145 xenograft model with negligible toxicity toward normal organs. Further investigations found that the Gln4 and Glu6 residues of P5 bind to FGFR2 to abolish its activation. Moreover, we developed the P5 cyclic derivative, DcP5, which achieved reinforced stability and anticancer activity in vivo. Our findings suggest P5 and its cyclic derivative DcP5 as potential candidates for anticancer therapy., Competing Interests: The authors declare that there is no conflict of interest., (© 2020 The Authors. MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

Foamed fly ash geopolymer was synthesized in this work to produce geopolymeric lightweight concrete (GLWC). Fly ash was activated by sodium silicate solution, and aluminum powder was employed as an in situ chemical foaming agent. The synthesized pastes were cured at 40 °C for 28 days, with bulk densities of resultant GLWCs ranging from 600 to 1600 kg/m 3 . The resulting mechanical properties, thermal conductivity, microstructure, and reaction product were fully characterized. Results show that GLWC had higher mechanical strength than commercial aerated concrete and developed 80-90% of its corresponding 28 days strength after curing for 7 days. For densities from 1200 to 600 kg/m 3 , the thermal conductivity diminished from 0.70 to 0.22 W/mK, which is much better than that of its counterpart, ordinary Portland cement (OPC). Scanning electron microscopy (SEM) images revealed decent matrices comprising geopolymeric gel and unreacted fly ash.

An accurate biomarker or method for diagnosis of thyroid nodule with indeterminate fine-needle aspiration result is essential for clinical treatment. Micro RNAs (miRNAs) of exosomes are advantageous in the diagnosis of tumors because they are highly stable, and be protected by a bilayer membrane structure. Exosomes were isolated from 13 papillary thyroid carcinoma (PTC) and 7 nodular goiter (NG) patients' plasma. Small RNA sequencing was performed on exosomes' RNA in next-generation sequencing (NGS) platform. Then, we performed comprehensive analysis on miRNA expression profile in exosome of two groups. One hundred and twenty-nine differentially expressed miRNAs were identified in plasma exosomes between PTC and NG patients. Forty-nine miRNAs were up-regulated, and 80 miRNAs were down-regulated in PTC patients. Receiver operating characteristic (ROC) curves of 129 miRNAs were plotted. Area under curve (AUC) of 129 miRNAs was 0.571-0.951, with distribution peak of 0.82-0.86. AUC of 11 miRNAs was above 0.9, miR-5189-3p had the most optimal performance for diagnosis between PTC and NG, with 0.951 of AUC. Target genes of 129 miRNAs were enriched into 7 cancer-related signaling pathways, including mitogen-activated protein kinase (MAPK), tumor necrosis factor (TNF), NF-kappa B signaling pathway and so on. This study profiled the miRNA signature of exosomes from PTC patients and NG patients. We proposed a group of miRNAs in plasma exosomes as candidate biomarkers for thyroid nodule diagnosis., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

A total of 15-30% of thyroid nodules that are evaluated by fine-needle aspiration are not clearly determined to be benign or malignant. Gene mutation analysis is recommended for the evaluation of thyroid nodules using clinical guidelines. The detection of circulating tumor DNA (ctDNA) has the potential to aid in the screening, diagnosis and prediction of thyroid cancer prognosis, and can be used when tissues are difficult to obtain. In the present study, whole-exome sequencing (WES) was performed on tumors and matched normal tissues from 10 patients with papillary thyroid carcinoma (PTC) in Quanzhou, China. Hotspot mutations in tumor DNA and cell-free DNA were identified in the validation cohort, which included 59 patients with PTC. BRAF V600E occurred in five samples, and was the most frequent mutation observed. Variation allele frequency (VAF) of BRAF V600E detected by WES was positively correlated with VAF determined using digital PCR (R 2 =0.9197; P=0.0099). A number of novel mutated genes were identified, including zinc finger protein 717, pleckstrin homology like domain family A member 1, RBMX like 3, lysine methyltransferase 5A and trichohyalin, along with the reported genes BRAF, NRAS and mucin 16, cell surface associated. Somatic mutated genes were enriched in the 'focal adhesion' pathway, as determined by Kyoto Encyclopedia of Genes and Genomes or Gene Ontology analysis. In the validation cohort, 44.07% of tumors were BRAF V600E-positive, and the sensitivity and specificity of BRAF V600E ctDNA were 61.54 and 90.91%, respectively. BRAF V600E was associated with aggressive tumor factors, including lymph node metastasis (P=0.001) and advanced disease stage (P=0.009). The present study investigated the accuracy of ctDNA detection in patients with PTC, and provided evidence that ctDNA can be used as an evaluation of tumor DNA in thyroid nodules., (Copyright: © Li et al.)

Tin-, iron-bearing tailing is a typically hazardous solid waste in China, which contains plenty of valuable tin, iron elements and is not utilized effectively. In this study, a multistage utilization process was put forward to get the utmost out of the valuable elements (tin and iron) from the tailings, and a gradient-recovery method with three procedures was demonstrated: (1) An activated roasting followed by magnetic separation process was conducted under CO-CO 2 atmosphere, tin and iron were efficiently separated during magnetic separation process, and 90.8 wt% iron was enriched in magnetic materials while tin entered into non-magnetic materials; (2) The tin-enriched non-magnetic materials were briquetted with CaCl 2 and anthracite and roasted, then tin-rich dusts were collected during the chloridizing roasting process; (3) The roasted briquettes were infiltrated in melting NaNO 3 to prepare NaNO 3 /C-PCMs by a infiltration method. Three kinds of products were obtained from the tailings by the novel process: magnetic concentrates containing 64.53 wt.% TFe, tin-rich dusts containg 52.4 wt.% TSn and NaNO 3 /C-PCMs for high temperature heat storage. Such a comprehensive and clean utilization method for tin-, iron-bearing tailings produced no secondary hazardous solid wastes, and had great potential for practical application.

Chromium was selectively recovered from ferronickel slag by roasting the slag with addition of Na 2 O 2 , followed by water leaching. The thermodynamic analysis revealed that in the presence of Na 2 O 2 at appropriate temperatures, the Cr 2 O 3 in the ferronickel slag can be converted to NaCrO 2 , instead of Na 2 CrO 4 , which prevents the formation of highly toxic Cr (VI). The experimental results confirmed that under the optimal alkaline roasting and water leaching conditions of the mass ratio of ferronickel slag to Na 2 O 2 of 1, roasting temperature of 600 °C, roasting time of 1 h, leaching temperature of 50 °C, leaching time of 1 h, and liquid-to-solid ratio of 10 mL/g, 92.33% of Cr was leached with 64.28% of Na and 11.16% of Si and only 0.06 wt % Cr was left in the leaching residue. The high leaching percentage of Cr was a result of the transformation of Cr 2 O 3 in the ferronickel slag to NaCrO 2 with a loose structure during alkaline roasting that was beneficial to water dissolution. Compared to the traditional alkaline roasting process, the proposed more environmentally friendly method did not produce toxic Cr (VI) during recovery of chromium and the resulting residue has potential to be used as a good construction material., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In this paper, we present a simple but effective label-free three dimensional (3D) microscopy for weakly absorbing samples. The proposed technique employs spatially-incoherent annular illumination to enhance absorption contrast of in-focus images and reduce phase contrast. We also employ mechanical scanning along axial direction to acquire a volume of the sample images. A 3D gradient operation is further adopted to remove the background with defocused shadows caused by oblique illumination. As such, a sequence of background-free sectioning images is acquired. The 3D gradient operation results in that only the structural edges of the weakly absorbing sample are visible in the images. We can therefore reconstruct the 3D skeleton structure of the sample from the sectioning image sequence. A label-free diatom is used to verify our technique experimentally. The 3D skeleton structure of the diatom is reconstructed and presented. The proposed technique would find applications in various fields, such as life science, materials science, etc., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Single-pixel imaging commonly uses a spatial light modulator (SLM) to encode a scene's spatial information into a one-dimensional light signal sequence so that a single-pixel detector can be used to capture a scene. Digital micromirror device, liquid crystal on silicon, or light emitted diode matrix is a common choice of SLM, but it requires a certain lens system in order to project the structured light pattern that is generated by the SLM onto the scene. Using a lens would not only lead to aberration but also result in difficulty for establishing a compact imaging system. Therefore, we propose to use a liquid crystal display (LCD) as an intensity-only SLM to conduct structured illumination. As such, single-pixel imaging can be performed in a lensless way. As an instance of the proposed technique, a small-size and multi-functional scanner is designed and established to prove the lensless single-pixel imaging concept. As experimentally demonstrated, the single-pixel scanner can not only achieve grayscale and true-color scanning as a typical scanner does, but also achieve distinctive functionalities, such as accurate optical character recognition from under-sampled data, on-the-fly encryption, and genuine document identification. This compact scanner is as thin as 2.48 millimeters. The proposed lensless single-pixel imaging technique might find applications in various fields.

A newly-developed platform, integrating subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH), was applied to analyze the clinical significance of circulating tumor cells (CTCs) for early screening of cancer in healthy people. The present case report describes one healthy individual who accepted a CTC peripheral blood test, and 8 CTCs/7.5 ml blood were detected. However, various conventional cancer biomarkers were all negative, including cervical cytological inspection, alpha-fetoprotein, cancer antigen (CA)-125, CA19-9, carcinoembryonic antigen (CEA), CA15-3 and human papilloma virus. To explore the origin of the CTCs, whole exome sequencing was used to analyze the CTC variation spectrum. A total of 42 mutations were associated with cancer according to analysis in COSMIC (http://cancer.sanger.ac.uk/cosmic). The results revealed a high risk of tumor in the colorectum, stomach and breast (13, 12 and 6 variations matched, respectively). In this individual, an intestinal polyp was discovered and removed by colonoscopy. The intestinal polyp was identified to be a hyperplastic polyp by pathological diagnosis. No lesions were discovered in the stomach and breast. No CTCs were detected in this patient's blood at 1 and 6 months after removal of the lesions. This case indicates that CTC detection by SE-iFISH has potential in early stage cancer screening, and the mutation spectrum of CTC assists the tracking of its sources.

Background/aims: How to aid recovery from severe skin injuries, such as burns, chronic or radiation ulcers, and trauma, is a critical clinical problem. Current treatment methods remain limited, and the discovery of ideal wound-healing therapeutics has been a focus of research. Functional recombinant proteins such as basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) have been developed for skin repair, however, some disadvantages in their use remain. This study reports the discovery of a novel small peptide targeting fibroblast growth factor receptor 2 IIIc (FGFR2IIIc) as a potential candidate for skin wound healing., Methods: A phage-displayed peptide library was used for biopanning FGFR2IIIc-targeting small peptides. The selected small peptides binding to FGFR2IIIc were qualitatively evaluated by an enzyme-linked immunosorbent assay. Their biological function was detected by a cell proliferation assay. Among them, an optimized small peptide named H1 was selected for further study. The affinity of the H1 peptide and FGFR2IIIc was determined by an isothermal titration calorimetry device. The ability of theH1 peptide to promote skin wound repair was investigated using an endothelial cell tube formation assay and wound healing scratch assay in vitro. Subsequently, the H1 peptide was assessed using a rat skin full-thickness wound model and chorioallantoic membrane (CAM) assays in vivo. To explore its molecular mechanisms, RNA-Seq, quantitative real-time PCR, and western blot assays were performed. Computer molecular simulations were also conducted to analyze the binding model., Results: We identified a novel FGFR2IIIc-targeting small peptide, called H1, with 7 amino acid residues using phage display. H1 had high binding affinity with FGFR2IIIc. The H1 peptide promoted the proliferation and motility of fibroblasts and vascular endothelial cells in vitro. In addition, the H1 peptide enhanced angiogenesis in the chick chorioallantoic membrane and accelerated wound healing in a rat full-thickness wound model in vivo. The H1 peptide activated both the PI3K-AKT and MAPK-ERK1/2 pathways and simultaneously increased the secretion of vascular endothelial growth factor. Computer analysis demonstrated that the model of H1 peptide binding to FGFR2IIIc was similar to that of FGF2 and FGFR2IIIc., Conclusion: The H1 peptide has a high affinity for FGFR2IIIc and shows potential as a wound healing agent. As a substitute for bFGF, it could be developed into a novel therapeutic candidate for skin wound repair in the future., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Our former study reported that Fe-Sn spinel (Fe 3-x Sn x O 4 ) was easily formed when SnO 2 and Fe 3 O 4 were roasted under CO-CO 2 atmosphere at 900-1100 °C. However, the formation procedure is still unclear and there is a lack of theoretical research on the formation mechanism of the Fe-Sn spinel. In this work, the reaction mechanisms between SnO 2 and Fe 3 O 4 under CO-CO 2 atmosphere were determined using XRD, VSM, SEM-EDS, XPS, etc. The results indicated that the formation of Fe 3-x Sn x O 4 could be divided into four steps: reduction of SnO 2 to solid phase SnO, volatilization of gaseous SnO, adsorption of gaseous SnO on the surface of Fe 3 O 4 , and redox reaction between SnO and Fe 3 O 4 . During the roasting process, part of Fe 3+ in Fe 3 O 4 was reduced to Fe 2+ by gaseous SnO, and meanwhile Sn 2+ was oxidized to Sn 4+ and entered into Fe 3-x Sn x O 4 . The reaction between SnO 2 and Fe 3 O 4 could be summarized as Fe 3 O 4  + xSnO (g)  → Fe 3-x Sn x O 4 (x = 0-1.0).

MicroRNA (miRNA)-25 is a small non-coding RNA that has been implicated in the tumorigenesis of many cancers, but little is known on the role of miR-25 in HCC metastasis. We hereby found that miR-25 was significantly upregulated in clinical HCC tissues compared with normal liver tissues. We also revealed that miR-25 dramatically stimulates HCC cell growth and activates the epithelial-mesenchymal transition (EMT). MiR-25 is activated by the WNT/β-catenin signaling pathway, and exerts its pro-metastatic function by directly inhibiting the Rho GDP dissociation inhibitor alpha (RhoGDI1). Downregulation of RhoGDI1 enhances expression of Snail, thereby promoting EMT. MiR-25 levels are positively correlated with β-catenin expression, whereas negatively correlated with the level of RhoGDI1 in HCC. Our findings provide new insights into the role of miR-25 in HCC metastasis, and implicate the potential application of miR-25 in HCC therapy.

Mammalian target of rapamycin (mTOR) is frequently upregulated in hepatocellular carcinoma (HCC). Blockage of mTOR was found to induce marked reduction in HCC growth in preclinical models. In the present study, we tested a novel mTOR inhibitor, Torin-2, for its antitumor efficacy in HCC cell lines Hep G2, SNU-182 and Hep 3B2.1-7. The HCC cell lines were cultured in vitro. These cells were treated with Torin-2. Cell apoptosis was evaluated by Annexin V staining. Cell proliferation and cell cycle progression were determined by Ki67 staining and propidium iodide staining, respectively. mTOR signaling, autophagy induction and expression of ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) were assessed by western blot analysis. The UHRF1 mRNA level was determined by real-time PCR. We found that Torin-2 effectively suppressed the growth and survival of HCC cell lines, demonstrated by reduced proliferation and a high rate of apoptosis. Further study elucidated that in addition to blocking mTOR complex 1 (mTORC1)-associated cell cycle progression and induction of autophagy, Torin-2 downregulated transcription of UHRF1, an essential regulator of DNA methylation that is highly expressed in HCC cell lines. Consistently, the level of DNA (cytosine-5)-methyltransferase 1 (DNMT1) was higher after treatment of the HCC cell lines with Torin-2. The downregulation of UHRF1 by Torin-1 was partially due to a decrease in the UHRF1 mRNA level. Torin-2 effectively inhibited HCC cell proliferation through induction of autophagy. Torin‑2-induced downregulation of UHRF1 expression may also contribute to its antitumor effect. Our research provides new clues regarding the antitumor effects of Torin-2 and sheds light on a novel therapeutic approach for HCC.

Many types of cancer have high antioxidant capacity that effectively scavenges reactive oxygen species and thus protect cancer cells against oxidative damage. The aim of this study was to examine the effect of 20 single nucleotide polymorphisms (SNPs) in 20 oxidative stress-related genes on clinical outcome in 219 patients with advanced non-small cell lung cancer (NSCLC) who were treated with EGFR tyrosine kinase inhibitors (TKIs). We assessed the associations of SNPs with prognosis in all patients as well as stratified by clinical characteristics. Three SNP (rs1695, rs2333227 and rs699512) were significantly associated with overall survival (OS). In a multivariate analysis, rs1695 AA and rs2333227 AG/GG genotypes were identified as independent prognostic factors for poor OS. Stratification analyses revealed that these 3 SNPs remained significantly associated with OS. Furthermore, there was a strong gene-dosage effect of these 3 SNPs on OS that patients with increasing number of unfavorable genotypes had significantly increased death risk. In conclusion, our findings provide the first evidence that genetic variants in oxidative stress-related genes may influence treatment outcome in advanced NSCLC patients receiving EGFR TKIs.