Constructing a disulfidptosis-related prognostic signature of hepatocellular carcinoma based on single-cell sequencing and weighted co-expression network analysis.

Hepatocellular carcinoma (HCC) ranks as the second leading cause of cancer-related deaths globally. Disulfidptosis is a newly identified form of regulated cell death that is induced by glucose starvation. However, the clinical prognostic characteristics of disulfidptosis-associated genes in HCC remain poorly understood. We conducted an analysis of the single-cell datasets GSE149614 and performed weighted co-expression network analysis (WGCNA) on the Cancer Genome Atlas (TCGA) datasets to identify the genes related to disulfidptosis. A prognostic model was constructed using univariate COX and Lasso regression. Survival analysis, immune microenvironment analysis, and mutation analysis were performed. Additionally, a nomogram associated with disulfidptosis-related signature was constructed to identify the prognosis of HCC patients. Patients with HCC in the TCGA and GSE14520 datasets were categorized using a disulfidptosis-related model, revealing significant differences in survival times between the high- and low-disulfidptosis groups. High-disulfidptosis patients exhibited increased expression of immune checkpoint-related genes, implying that immunotherapy and certain chemotherapies may be beneficial for them. Meanwhile, the ROC and decision curves analysis (DCA) indicated that the nomogram has satisfying prognostic efficacy. Moreover, the experimental results of GATM in this prognostic model indicated that GATM is low expressed in HCC tissues, and GATM knockdown promotes the proliferation and migration of HCC cells. By analyzing single-cell and bulk multi-omics sequencing data, we developed a prognostic signature related to disulfidptosis and explored the relationship between high- and low-disulfidptosis groups in HCC. This study offers a novel reference for gaining a deeper understanding of the role of disulfidptosis in HCC.

Study of Hydroxyapatite-coated High-strength Biodegradable Magnesium-based Alloy in Repairing Fracture Damage in Rats.

BACKGROUND/AIM: Hydroxyapatite (HA) coating can improve the degradation rate and biological activity of metallic implants. This study aimed to fabricate a hydroxyapatite-coated ultrafine-grained biodegradable WE43 magnesium (HA/UFG-WE43 Mg) implant for repairing bone fractures. MATERIALS AND METHODS: A hybrid approach, including parallel tubular-channel angular pressing (PTCAP) and physical vapour deposition (PVD) magnetron sputtering, was employed. The HA/UFG-WE43 Mg samples were tested in terms of their physicochemical and biological properties. RESULTS: The processed tubes exhibited ultrafine structures and the uniformity of microstructures improved following the two-pass PTCAP. The phase composition of the coating formed on UFG-WE43 Mg implant at 250 W for 90 min after heat treatment at 500°C for 60 min confirmed the presence of the HA characteristic peaks. Rat skeletal muscle cells were inoculated on the specimens and cultured for 1, 2, 6, 12, and 24 h, followed by evaluation of cell adhesion and morphology. The growth rates of cells were examined by the Cell Counting Kit8 (CCK-8) and cell survival was observed after 3 days of culture by fluorescence microscopy. The concentration of Mg ions in the blood of rats on 1, 3, 5, 7, and 15 days showed a reduction in Mg concentration after deposition of HA. CONCLUSION: Combination of PTCAP processing followed by surface modification led to tibial fracture healing, and histological analysis of implanted areas demonstrated an efficient biodegradation of the implanted material and a moderate inflammatory reaction.

Berberine protects against palmitate induced beta cell injury via promoting mitophagy.

BACKGROUND: Destruction of pancreatic beta cells is the most typical characteristic of diabetes. OBJECTIVE: We aimed to evaluate the effect of berberine (BBR), a bioactive isoquinoline derivative alkaloid, on beta cell injury. METHODS: Rodent pancreatic beta cell line INS-1 was treated with 0.5 mM palmitate (PA) for 24 h to establish an in vitro beta cell injury model. RESULTS: BBR at 5 µM promoted cell viability, inhibited cell apoptosis and enhanced insulin secretion in PA-induced INS-1 cells. BBR treatment also suppressed PA-induced oxidative stress in INS-1 cells, as evidenced by the decreased ROS production and increased activities of antioxidant enzymes. In addition, suppressed ATP production and reduced mitochondrial membrane potential were restored by BBR in PA-treated INS-1 cells. It was further determined that BBR affected the expressions of mitophagy-associated proteins, suggesting that BBR promoted mitophagy in PA-exposed INS-1 cells. Meanwhile, we found that BBR facilitated nuclear expression and DNA-binding activity of Nrf2, an antioxidative protein that can regulate mitophagy. Finally, a rescue experiment was performed and the results demonstrated that the effect of BBR on cell viability, apoptosis and mitochondrial function in PA-induced INS-1 cells were cancelled by PINK1 knockdown. CONCLUSIONS: BBR protects islet ß cells from PA-induced injury, and this protective effect may be achieved by regulating mitophagy. The present study may provide a novel therapeutic strategy for ß cell injury in diabetes mellitus.

Mechanism analysis of the immobilization of heavy metal ions with the water-soluble polymer: The influence of resin structure and the further adsorption of chelate.

Polymer materials have become one of the potential materials for remediation of heavy metal (HM) contamination in water and soil. However, the specific advantages of polymers are rarely studied. Water-soluble thiourea formaldehyde resin (WTF) is one of the effective polymer amendments. Through leaching experiments, WTF can stabilize 93.0% of Cd2+ and 99.7% of Cu2+. The results of HM morphology analysis show that after adding WTF, most of the HMs have been transformed into a relatively stable state. For example, in the process of remediation of 6 mg/kg Cd contaminated soil, the proportion of acid-soluble Cd decreased from 56.5% to 12.8%, and the residual state increased from 13.5% to 45.4%. Compared with the resin-free structure, the three-dimensional structure of the resin plays an important role, but the efficiency of precipitation with HMs is doubled. According to the simulation of the adsorption process by Materials Studio, the characterization of the scanning electron microscope-energy dispersive instrument and the results of the adsorption experiment, in the solution, the precipitate formed by WTF and Cd2+ has multilayer adsorption of HMs, and can further adsorb HM by -OH. Soil enzyme activity experiments proved that the risk of secondary pollution by adding WTF is rare, and even WTF can achieve the effect of slow-release nitrogen fertilizer. In the WTF remediation process, the biological toxicity reduction of HMs is result from, on the one hand, the complexation of functional group of WTF; on the other hand, the resin structure of WTF; in addition, multi-layer adsorption and adsorption of end groups in the precipitation formed by WTF and HM. This work provides a theoretical basis for the potential capabilities of water-soluble resins and is beneficial to the design and development of subsequent amendments.

Bisabolanoic acid A, a new polychiral sesquiterpene with AChE inhibitory activity from a mangrove-derived fungus Colletotrichum sp.

A new polychiral bisabolane sesquiterpene, bisabolanoic acid A (1), was isolated from the mangrove-derived fungus Colletotrichum sp. SCSIO KcB3-2. Its planar structure was identified on the basis of spectroscopic data analysis (HRESIMS, 1D, and 2D NMR), and the absolute configurations of three chiral carbons were determined by experimental and calculated electronic circular dichroism (ECD) and optical rotatory dispersion (ORD), together with Mo2(OAc)4-induced ECD methods. Bisabolanoic acid A (1) showed moderate inhibitory activity against acetylcholinesterase (AChE) with IC50 value of 2.2 µM, and the in silico molecular docking was also performed.

Risk factors of postoperative bone cement leakage on osteoporotic vertebral compression fracture: a retrospective study.

PURPOSE: To investigate risk factors of bone cement leakage in percutaneous vertebroplasty(PVP)for osteoporotic vertebral compression fracture (OVCF). METHODS: A total of 236 patients (344 vertebrae) who underwent PVP between November 2016 and June 2020 were enrolled in the study. Clinical and radiological characteristics, including age, gender, course of disease, trauma, type of vertebral fracture, cortical continuity of vertebral body, intervertebral vacuum cleft (IVC), fracture severity, fracture level, basivertebral foramen, bone cement dispersion types, the cement injection volume, the type of cement leakage, puncture approach, and intrusion of the posterior wall, were considered as potential risk factors. Three types of leakage (type-B, type-C, and type-S) were defined and risk factors for each type were analyzed. Logistic analysis was used to study the relationship between each factor and the type of cement leakage. RESULTS: The incidences of the three types of leakage were 28.5%, 24.4%, and 34.3%. The multinomial logistic analysis revealed that the factors of type-B leakage were the shape of cement and basivertebral foramen. One significant factor related to type-C leakage was cortical disruption, and the factors of type-S leakage were bone cement dispersion types, basivertebral foramen, cleft, fracture severity, an intrusion of the posterior wall, and gender. CONCLUSION: Different types of cement leakage have their own risk factors, and the analysis of risk factors of these might be helpful in reducing the rate of cement leakage.

Effect of water-soluble thiourea formaldehyde (WTF) on soil contaminated with high copper (â ¡) concentration.

It is very important to seek a heavy metal soil stabilization/solidification (S/S) agent that has less risk of secondary release and has less impact on the soil. This study explored the repair effect of a new resin repair agent water-soluble thiourea-formaldehyde (WTF), and its stability under indigenous biodegradation and compared the repair effect with sodium sulfide (Na2S) and hydroxyapatite (HAP). Diethylene triamine pentaacetic acid leaching experiments show that WTF can effectively solidify/stabilize 97.9-84.7% of Cu. At the same time, heavy metal speciation analysis experiments show that WTF does indeed convert the exchangeable Cu in the soil into a non-exchangeable form. Research on soil organic matter, biological carbon and enzyme activity after remediation shows that WTF has a more positive effect on soil function, compared with HAP and Na2S. Experiments using indigenous microorganisms to decompose the precipitation formed by WTF and Cu show that under the condition of less impact on soil microorganisms, the risk of secondary release of heavy metals caused by soil microorganisms after WTF remediation is less. These findings provide valuable experience for understanding the role of resin structure in preventing the secondary release of heavy metals and restoring soil function.

NLRX1 alleviates lipopolysaccharide-induced apoptosis and inflammation in chondrocytes by suppressing the activation of NF-κB signaling.

Osteoarthritis (OA) is a chronic debilitating disease characterized by joint degeneration. Excessive chondrocyte apoptosis and inflammation contributes to articular cartilage destruction in OA pathology. Nucleotide-binding oligomerization domain (NOD)-like receptor X1 (NLRX1) has emerged as a critical regulator of inflammation that participates in the pathology of diverse diseases. To date, little is known about the role of NLRX1 in OA. In the present study, we aimed to explore the function of NLRX1 in lipopolysaccharide (LPS)-induced injury in chondrocytes, an in vitro model of OA. NLRX1 mRNA was detected by quantitative polymerase chain reaction (qPCR) analysis. Protein expression of NLRX1, phosphorylated IκB kinase ß (IKKß), and phosphorylated nuclear factor-κB (NF-κB) p65 were examined by western blot. Cell viability was assessed by the MTT assay. Cell apoptosis was evaluated by measuring caspase-3 activity. Cytokine release was assessed by enzyme-linked immunosorbent assay (ELISA). NF-κB signaling activation was analyzed with a luciferase reporter assay. Herein, our results revealed that NLRX1 expression was markedly decreased in LPS-treated chondrocytes. Functional experiments demonstrated that NLRX1 overexpression significantly improved cell viability and attenuated LPS-treated chondrocyte apoptosis and inflammation, while NLRX1 silencing caused the opposite effects. Moreover, our results showed that NLRX1 regulated LPS-induced NF-κB signaling activation. Notably, NF-κB signaling inhibition significantly reversed the NLRX1-knockdown-mediated enhanced effects on LPS-induced apoptosis and inflammation. Overall, these results demonstrate that NLRX1 alleviates LPS-induced apoptosis and inflammation in chondrocytes by negatively regulating NF-κB signaling, results that indicate an anti-inflammatory role for NLRX1 in OA. Our findings suggest that NLRX1 may serve as a potential therapeutic target for OA.

Long non-coding RNA PVT1, a molecular sponge for miR-149, contributes aberrant metabolic dysfunction and inflammation in IL-1ß-simulated osteoarthritic chondrocytes.

Osteoarthritis (OA), a common form of degenerative joint disease, is typified by inflammatory response and the loss of cartilage matrix. Long non-coding RNAs (lncRNAs) are emerging as a new player in gene regulation and exert critical roles in diverse physiologic and pathogenic processes including OA. The lncRNA plasmacytoma variant translocation 1 (PVT1) has been implicated in cancer, diabetes and septic acute kidney injury. Recent research confirmed the elevation of PVT1 in patients with OA. However, its role in the development of OA remains poorly elucidated. In the present study, high expression of PVT1 was observed in cartilage of OA patients and IL-1ß-stimulated chondrocytes. Moreover, cessation of PVT1 expression dramatically reversed the inhibition of IL-1ß on collagen II and aggrecan expression, but suppressed IL-1ß-induced elevation of matrix metalloproteinases (MMPs), including MMP-3, MMP-9 and MMP-13. Simultaneously, PVT1 inhibition also antagonized the production of inflammatory cytokines upon IL-1ß stimulation, including prostaglandin E2 (PGE2), NO, IL-6, IL-8 and TNF-α. Further molecular mechanism analysis identified PVT1 as an endogenous sponge RNA that could directly bind to miR-149 and repress its expression and activity. More importantly, miR-149 inhibition reversed the protective roles of PVT1 cessation in attenuating IL-1ß-evoked matrix aberrant catabolism and inflammation. Together, this research confirms that lowering PVT1 expression may ameliorate the progression of OA by alleviating cartilage imbalance toward catabolism and inflammatory response, thus supporting a promising therapeutic strategy against OA.

Assessment of water-soluble thiourea-formaldehyde (WTF) resin for stabilization/solidification (S/S) of heavy metal contaminated soils.

Stabilization/Solidification (S/S) can be regarded as necessary for remediation of heavy metal contaminated soil. There is, however, solid agent is not very convenient to use. Water-soluble thiourea-formaldehyde (WTF) is a novel chelating agent, which has more practical applications. The process of WTF resin for S/S process of heavy metal contaminated soils was studied. Laboratory-prepared slurries, made of field soils spiked with Cd2+ and Cr6+ were treated with WTF resin. The toxicity characteristic leaching procedure (TCLP) showed that with 2 wt% WTF, in the neutral condition of soil after treatment for 7 d, the leaching concentrations of Cd2+ and Cr6+ in contaminated soil were decreased by 80.3% and 92.6% respectively. Moreover, Tessier sequence extraction procedure showed WTF resin reduced the leaching concentration by transforming heavy metal from exchange form to organic form. The structure of WTF is obtained according to elemental analysis result and reaction mechanism. Through analysis of the infrared spectrogram of WTF and WTF heavy mental chelating precipitation, WTF can form stable chelate with heavy mental through coordination. The significant groups are hydroxyl, nitrogen and sulphur function groups in WTF mainly. Toxicology test revealed that the WTF resin is nontoxic to microorganism in the soils.

Synthesis of a water-soluble thiourea-formaldehyde (WTF) resin and its application to immobilize the heavy metal in MSWI fly ash.

Because of the high concentrations of heavy metals, municipal solid waste incineration (MSWI) fly ash is classified as a hazardous waste, which need to be treated to avoid damaging the environment. A novel water-soluble thiourea-formaldehyde (WTF) resin was synthesized by two step reactions (hydroxymethylation reaction and condensation reaction) in the laboratory. Synthetic conditions, removal of free formaldehyde in the resin and the ability of immobilization heavy metals in the MSWI fly ash were studied. The possible molecular structure of the resin was also discussed by elemental analysis and FTIR spectra. Experimental results showed that the synthesis conditions of WTF resin were the formaldehyde/thiourea (T/F) mole ratio of 2.5:1, hydroxymethylation at pH 7.0-8.0 and 60 °C for 30min, and condensation of at pH 4.5-5.0 and 80 °C. In addition, the end point of condensation reaction was measured by turbidity point method. The result of elemental analysis and FTIR spectra indicated that thiourea functional group in the WTF resin chelated the heavy metal ions. Melamine can efficiently reduce the free formaldehyde content in the resin from 8.5% to 2%. The leaching test showed that the immobilization rates of Cr, Pb and Cd were 96.5%, 92.0% and 85.8%, respectively. Leaching concentrations of Cr, Pb and Cd in the treated fly ash were decreased to 0.08 mg/L, 2.44 mg/L and 0.23 mg/L, respectively. The MSWI fly ash treated by WTF resin has no harm to the environment.

An anaerobic two-layer permeable reactive biobarrier for the remediation of nitrate-contaminated groundwater.

In this paper, an anaerobic two-layer permeable reactive biobarrier system consisting of an oxygen-capturing layer followed by a biodegradation layer was designed firstly for evaluating the remediation effectiveness of nitrate-contaminated groundwater. The first layer filling with granular oxygen-capturing materials is used to capture dissolved oxygen (DO) in groundwater in order to create an anaerobic condition for the microbial denitrification. Furthermore, it can also provide nutrition, such as carbon and phosphorus, for the normal metabolism of immobilized denitrifying bacteria filled in the second layer. The second layer using granular activated carbon as microbial carrier is able to biodegrade nitrate entering the barrier system. Batch experiments were conducted to identify the effect of DO on microbial denitrification, oxygen-capturing performance of zero valent iron (ZVI) powder and the characteristics of the prepared oxygen-capturing materials used to stimulate growth of denitrifying bacteria. A laboratory-scale experiment using two continuous upflow stainless-steel columns was then performed to evaluate the feasibility of this designed system. The first column was filled with granular oxygen-capturing materials prepared by ZVI powder, sodium citrate as well as other inorganic salts, etc. The second column was filled with activated carbon immobilizing denitrifying microbial consortium. Simulated nitrate-contaminated groundwater (40 mg NO3-N/L, pH 7.0) with 6 mg/L of DO content was pumped into this system at a flow rate of 235 mL/d. Samples from the second column were analyzed for nitrate and its major degradation byproduct. Results showed that nitrate could be removed more than 94%, and its metabolic intermediate, nitrite, could also be biodegraded further in this passive system. Further study is necessary in order to evaluate performance of its field application.

[Synthesis and optical properties of Nd(III) perfluoro-carboxylate complexes with 2,2'-bipyridine].

A series of neodymium complexes, Nd(CF3COO)3 x Dipy, Nd(C2F5 COO)3 x Dipy and Nd(C3F7COO)3 x Dipy were synthesized and characterized by FTIR spectra, elemental analysis, thermogravimetric analysis, UV-Vis-NIR absorption spectra and PL spectra. The decomposition temperature was found to be more than 260 C and maximum weight losses rates above 340 degrees C which indicate that they have good thermal stability. The low vibrational energy C-F bonds were used to replace the C-H bonds in organic group for improving the optical properties of materials. The length of carbon chain and the coordination structure of Nd(III) affect the absorption transition strength. According to the UV-Vis-NIR absorption spectra, the Judd-Ofelt parameters were calculated and the radiative properties were also presented. The stimulated emission cross-sections of the Nd(CF3COO)3 x Dipy, Nd(C2F5COO)3 x Dipy and Nd(C3FCOO)3 x Dipy were 3.63 x 10(-20), 2.36 x 10(-20) and 1.49 x 10(-20) cm2 respectively, which were as good as some reported inorganic materials. These complexes will be a series of promising materials for liquid laser application.

Laboratory column study for remediation of MTBE-contaminated groundwater using a biological two-layer permeable barrier.

In this study, an in situ biological two-layer permeable reactive barrier system consisting of an oxygen-releasing material layer followed by a biodegradation layer was designed to evaluate the remediation effectiveness of MTBE-contaminated groundwater. The first layer containing calcium peroxide (CaO(2)) and other inorganic salts is to provide oxygen and nutrients for the immobilized microbes in the second layer in order to keep them in aerobic condition and maintain their normal metabolism. Furthermore, inorganic salts such as potassium dihydrogen phosphate (KH(2)PO(4)) and ammonium sulphate ((NH(4))(2)SO(4)) can also decrease the high pH caused by the alkali salt degraded from CaO(2). The second layer using granular expanded perlite as microbial carrier is able to biodegrade MTBE entering the barrier system. Batch experiments were conducted to identify the appropriate components of oxygen-releasing materials and the optimum pH value for the biodegradation of MTBE. At pH=8.0, the biodegradation efficiency of MTBE is the maximum and approximately 48.9%. A laboratory-scale experiment using two continuous upflow stainless-steel columns was then performed to evaluate the feasibility of this designed system. The fist column was filled with oxygen-releasing materials at certain ratio by weight. The second column was filled with expanded perlite granules immobilizing MTBE-degrading microbial consortium. Simulated MTBE-contaminated groundwater, in which dissolved oxygen (DO) content was 0mg/L, was pumped into this system at a flow rate of 500mL/d. Samples from the second column were analyzed for MTBE and its major degradation byproduct. Results showed that MTBE could be removed, and its metabolic intermediate, tert-butyl alcohol (TBA), could also be further degraded in this passive system.