Turning sublimed sulfur and bFGF into a nanocomposite to accelerate wound healing via co-activate FGFR and Hippo signaling pathway.

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.

Acesulfame potassium triggers inflammatory bowel disease via the inhibition of focal adhesion pathway.

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.

Lian-Mei-Yin formula alleviates diet-induced hepatic steatosis by suppressing Yap1/FOXM1 pathway-dependent lipid synthesis.

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.

Prediction model of cervical lymph node metastasis based on clinicopathological characteristics of papillary thyroid carcinoma: a dual-center retrospective study.

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.

Detoxication and recycling of chromium slag and C-bearing dust via composite agglomeration process (CAP)-blast furnace method.

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)2O4 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.

SAIF plays anti-angiogenesis via blocking VEGF-VEGFR2-ERK signal in tumor treatment.

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.

A novel high activity MnXFe3-XO4 spinel catalyst for selective catalytic reduction of NO using NH3 prepared by a short process from natural minerals for low-temperature sintering flue gas: Effect of X value on catalytic mechanism.

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 MnXFe3-XO4 for the NH3 selective catalytic reduction of NO (NH3-SCR) reaction, i.e., the Mn, Fe ratio, and then prepared a novel highly active mineral-based pure phase MnXFe3-XO4 spinel NH3-SCR catalyst by natural ferromanganese ore fines with iron-red fines (Fe2O3) 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 (Mn1.5Fe1.5O4) is the best for NH3-SCR reaction. Mn1.5Fe1.5O4 nano-particles (201 nm) has nearly 100 % NO conversion (with 5 % H2O(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 NH3-SCR reaction with increasing X value at the MnXFe3-XO4 surface.

CH02 peptide promotes ex vivo expansion of umbilical cord blood-derived CD34 + hematopoietic stem/progenitor cells.

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.

Inhibition of FGFR2 Signaling by Cynaroside Attenuates Liver Fibrosis.

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 (CCl4) 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.

FGFR4 and EZH2 inhibitors synergistically induce hepatocellular carcinoma apoptosis via repressing YAP signaling.

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.

Mn-Doped Spinel for Removing Cr(VI) from Aqueous Solutions: Adsorption Characteristics and Mechanisms.

In this study, the manganese (Mn) was doped in the MnFe2O4 crystal by the solid-phase synthesis method. Under the optimum conditions (pH = 3), the max removal rate and adsorption quantity of Cr(VI) on MnFe2O4 adsorbent obtain under pH = 3 were 92.54% and 5.813 mg/g, respectively. The DFT calculation results indicated that the adsorption energy (Eads) between HCrO4- and MnFe2O4 is -215.2 KJ/mol. The Cr(VI) is mainly adsorbed on the Mn atoms via chemical bonds in the form of HCrO4-. The adsorption of Mn on the MnFe2O4 surface belonged to chemisorption and conformed to the Pseudo-second-order equation. The mechanism investigation indicated that the Mn in MnFe2O4 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 MnFe2O4 via chemisorption. The Mn in MnFe2O4 can form ionic bonds with the O atoms of HCrO4-/CrO42-, 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 MnFe2O4 surface in the form of Cr(OH)3 colloids, which can be separated by magnetic separation.

NKD2 Trigger NF-κB Signaling Pathway and Facilitates Thyroid Cancer Cell Proliferation.

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.

Turning gray selenium and sublimed sulfur into a nanocomposite to accelerate tissue regeneration by isothermal recrystallization.

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.

Hyaluronic acid-FGF2-derived peptide bioconjugates for suppression of FGFR2 and AR simultaneously as an acne antagonist.

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.

One-step separation of tin from e-waste by a chemical vapor transport process (CVT): Preparation of nano-SnO2.

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-SnO2. The effect of roasting parameters on Sn volatilization and characterization of nano-SnO2 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-CO2-N2 atmosphere. In addition, nano-SnO2 with a crystallinity of 99.9 %, an average grain size of 24.8 nm and a specific surface area of 97.9 m2/g was synthesized successfully.

Triclocarban triggers osteoarthritis via DNMT1-mediated epigenetic modification and suppression of COL2A in cartilage tissues.

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.

Formation and Inhibition Mechanism of Na8SnSi6O18 during the Soda Roasting Process for Preparing Na2SnO3.

To produce Na2SnO3, 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 (Na8SnSi6O18) was easily formed due to the main gangue of quartz in cassiterite concentrates, which was almost insoluble and decreased the quality of Na2SnO3. The formation and transitions of Na8SnSi6O18 in the SnO2-SiO2-Na2CO3 system roasted under a CO-CO2 atmosphere were determined. The results indicated that the formation of Na8SnSi6O18 could be divided into two steps: SnO2 reacted with Na2CO3 to form Na2SnO3, and then Na2SnO3 was rapidly combined with SiO2 and Na2CO3 to form low melting point Na8SnSi6O18. In addition, Na8SnSi6O18 can be decomposed into Na2SiO3 and Na2SnO3 by using excess Na2CO3.