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Objectives: This study aims to clarify the effect of ferroptosis by P. gingivalis on periodontal epithelium impairment and potential mechanisms., Materials and Methods: The expression of epithelial junction proteins (CDH1, OCLN, ZO-1), FTL and GPX4 in healthy and periodontitis tissues was analyzed using bioinformatics analysis and validated in vivo. An in vitro model was constructed to evaluate ferroptosis by mitochondria morphology, content of iron and GSH, and level of lipid peroxidation, FTL, GPX4 and SLC7A11. The iron concentration was changed with iron chelator DFO and iron supplementation FAC. The epithelial impairment was assessed by protein expression. To investigate the mechanism, si-MYB (a negative transcription factor of SLC7A11) and GPX4 inhibitor RSL3 were employed., Results: CDH1, OCLN, ZO-1 and GPX4 expression was decreased, while FTL expression was elevated in periodontitis tissues. Infected cells showed ferroptosis change of the mitochondria with higher level of lipid peroxidation, iron, FTL and lower level of GPX4, GSH, SLC7A11. FAC augmented ferroptosis and weakened epithelial junction, while DFO exhibited a counteractive effect. Silencing MYB rescued SLC7A11, GPX4 and epithelial junction proteins, which was hindered by RSL3., Conclusions: Our study demonstrated that P. gingivalis weakened the oral epithelial barrier by causing ferroptosis via inhibiting SLC7A11/GSH/GPX4 axis., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Prior studies have revealed an increased susceptibility to epilepsy in hyperthyroid individuals, but the genetic basis of the hyperthyroidism-epilepsy relationship is not fully comprehended, prompting this study to explore this potential association. We conducted a two-sample Mendelian randomization (TSMR) study to explore the relationship between hyperthyroidism and epilepsy by utilizing aggregated statistics from Genome-Wide Association Studies (GWAS). Data for hyperthyroidism were derived from a GWAS encompassing 462,933 participants, while epilepsy data were sourced from the International League Against Epilepsy (ILAE) consortium. Five distinct methods were employed for TSMR analysis, which included the inverse variance weighting method, MR Egger method, weighted median method, simple model, and weighted model. In our sensitivity analysis, we employed the MR Egger and MR PRESSO methods to assess pleiotropy, and inverse variance weighting and MR Egger in Cochran's Q statistics to assess heterogeneity. In the IEU database, utilizing the MR-Egger method, we obtained an odds ratio (OR) of 2.631 (95% CI 0.608, 9.796) with a p-value of 0.122. Meanwhile, employing the Weighted Median method yielded an OR of 1.813 (95% CI 0.786, 4.181) with a p-value of 0.163. The IVW method exhibited an OR of 1.986 (95% CI 1.127, 3.502) with a p-value of 0.018. In the assessment of heterogeneity, the MR-Egger method produced a Q statistic of 65.205, accompanied by a p-value of 0.087, while the IVW method recorded a Q statistic of 66.668 with a p-value of 0.083. The multifactorial analysis results showed an intercept term with a standard error (SE) value of 0.009 and a p-value of 0.291. In the FinnGen database, employing the MR-Egger method for all epilepsy data, we observed an OR of 0.952 (95% CI 0.831, 1.093) with a p-value of 0.539. Simultaneously, the Weighted Median method produced an OR of 0.986 (95% CI 0.953, 1.021) with a p-value of 0.423. The IVW method indicated an OR of 0.992 (95% CI 0.965, 1.019) with a p-value of 0.541. The MR-Egger method's assessment of heterogeneity resulted in a Q statistic of 2.671, associated with a p-value of 0.445, while the IVW method generated a Q statistic of 3.011 with a p-value of 0.556. The multifactorial analysis results displayed an intercept term with a SE-value of 0.019 and a p-value of 0.601. Sensitivity analysis found no evidence of horizontal pleiotropy or heterogeneity. Hyperthyroidism was found to be causally related to all epilepsy but had no effect on other types of epilepsy., (© 2024. The Author(s).)

Background: Epilepsy's pathogenesis and progression are significantly influenced by neuroinflammation, blood-brain barrier function, and synaptic remodeling function. Matrix metalloproteinase 9 (MMP-9), as a critical factor, may contribute to the development of epilepsy through one or more of the above-mentioned pathways. This study aims to evaluate and quantify the correlation between MMP-9 levels and epilepsy., Methods: We conducted a comprehensive search of Embase, Web of Science, PubMed, Cochrane Library, WanFang DATA, VIP, and the CNKI to identify studies that investigate the potential association between MMP-9 and epilepsy. The data were independently extracted by two researchers and assessed for quality using the Cochrane Collaboration tool. The extracted data were analyzed using Stata 15 and Review Manager 5.4. The study protocol was registered prospectively at PROSPERO, ID: CRD42023468493., Results: Thirteen studies with a total of 756 patients and 611 matched controls met the inclusion criteria. Eight of these studies reported total serum MMP-9 levels, and the other five studies were used for a further subgroup analysis. The meta-analysis indicated that the serum MMP-9 level was higher in epilepsy patients (SMD = 4.18, 95% confidence interval = 2.18-6.17, p  < 0.00001) compared with that in the control group. Publication bias was not detected according to Begg's test. The subgroup analysis of country indicated that the epilepsy patients in China, Poland, and Egypt had higher levels of serum MMP-9 than the control group, with the increase being more pronounced in Egypt. The subgroup analysis of the age category demonstrated that the serum MMP-9 levels of the adult patients with epilepsy were significantly higher than those of the matched controls. However, the serum MMP-9 levels did not significantly differ in children with epilepsy. The subgroup analysis of the seizure types demonstrated substantial difference in the MMP-9 levels between patients of seizure-free epilepsy (patients who have been seizure-free for at least 7 days) and the control group. Meanwhile, the serum MMP-9 level in patients with epileptic seizures was significantly higher than that in the control group. The subgroup analysis based on seizure duration in patients showed that the serum MMP-9 levels at 1-3, 24, and 72 h after seizure did not exhibit significant differences between female and male patients with epilepsy when compared with the control group. The serum MMP-9 levels at 1-3 and 24 h were significantly higher than those of the matched controls. Nevertheless, the serum MMP-9 level at 72 h was not significantly different from that in the control group., Conclusion: This meta-analysis presents the first comprehensive summary of the connection between serum MMP-9 level and epilepsy. The MMP-9 levels in epilepsy patients are elevated. Large-scale studies with a high level of evidence are necessary to determine the exact relationship between MMP-9 and epilepsy., 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 © 2024 Wang, Lin, Yao, Liu, Chen and Diao.)

Objective: The current study is conducted to investigate the potential prognostic value of the age-male-albumin-bilirubin-platelets (aMAP) score in breast cancer patients with liver metastasis after surgery., Methods: This is a retrospective study of 178 breast cancer patients who developed liver metastasis after surgery. These patients were treated and followed up from 2000 to 2018 at our hospital. The aMAP risk score was estimated in accordance with the following formula: . The optimal cutoff value of the aMAP was evaluated via X-tile. Kaplan-Meier, Log-rank and Cox proportional hazards regression models were applied to determine the clinical influence of the aMAP score on the survival outcomes. The nomogram models were established by multivariate analyses. The calibration curves and decision curve analysis were applied to evaluate the estimated performance of the nomogram models., Results: A total of 178 breast cancer patients were divided into low aMAP score group (<47.6) and high aMAP score group (≥47.6) via X-tile plots. The aMAP score was a potential prognostic factor in multivariate analysis. The median disease free survival (p=0.0013) and overall survival (p=0.0003) in low aMAP score group were longer than in high aMAP score group. The nomograms were constructed to predict the DFS with a C-index of 0.722 (95% CI, 0.673-0.771), and the OS with a C-index of 0.708 (95% CI, 0.661-0.755). The aMAP-based nomograms had good predictive performance., Conclusion: The aMAP score is a potential prognostic factor in breast cancer with liver metastasis after surgery. The aMAP score-based nomograms were conducive to discriminate patients at high risks of liver metastasis and develop adjuvant treatment and prevention strategies., Competing Interests: The authors declare no conflict of interest., (© 2024 Chen et al.)

The reaction mechanism underpinning the operation of K-O 2 batteries, particularly the O 2 reactions at the positive electrode, is still not completely understood. In this work, by combining in situ Raman spectroelectrochemistry and density functional theory calculations, we report on a fundamental study of K-O 2 electrochemistry at a model interface of Au electrode/DMSO electrolyte. The key products and intermediates (O 2 - , KO 2 and K 2 O 2 ) are identified and their dependency on the electrode potential is revealed. At high potentials, the first reduction intermediate of O 2 - * radical anions (* denotes the adsorbed state) can desorb from the Au electrode surface and combine with K + cations in the electrolyte producing KO 2 via a solution-mediated pathway. At low potentials, O 2 can be directly reduced to on the Au electrode surface, which can be further reduced to at extremely low potentials. The fact that K 2 O 2 has only been detected in the very high overpotential regime indicates a lack of KO 2 disproportionation reaction both on the Au electrode surface and in the electrolyte solution. This work addresses the fundamental mechanism and origin of the high reversibility of the aprotic K-O 2 batteries.

Objective: This study aims to investigate the potential prognostic value of albumin-bilirubin (ALBI) score in breast cancer patients with liver metastasis after surgery., Methods: This was a retrospective study of 178 breast cancer patients with liver metastasis after surgery. ALBI score was calculated by the following formula: (log10 bilirubin × 0.66) - (albumin × 0.085). The optimal cutoff value of ALBI score was assessed by X-tile. The clinical influence of ALBI score on survival outcomes using Kaplan-Meier method, Log-rank test, Cox proportional hazards regression model. The calibration curves, decision curve analysis and time-dependent ROC curve were used to assess the predictive performance of the nomogram's models., Results: The classifications of 178 breast cancer patients with liver metastasis after surgery were as follows: low ALBI score group (＜-3.36) vs. high ALBI score group (≥-3.36). The Cox proportional hazards regression model indicated that ALBI score was a potential predictor. Kaplan-Meier survival curve performed that the median disease free survival (p = 0.0029) and overall survival (p＜0.0001) in low ALBI score group were longer than in high ALBI score group. The ALBI-based nomograms had good predictive performance., Conclusions: The ALBI score has high prognostic ability for survival time in breast cancer with liver metastasis after surgery. These models will be valuable in discriminating patients at high risks of liver metastasis., 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: American Academy of Orthopaedic Surgeons (AAOS) has provided the guidelines for diagnosing a patient with periprosthetic joint infection including the use of positron emission tomography/computed tomography (PET/CT). Systematic evidence focussing on periprosthetic joint infection (PJI) of hip is limited, which also contains limited number of studies. Hence, the current study aims to perform a pooled analysis of all studies that have assessed the diagnostic accuracy of PET/CT for PJI of hip., Methods: Searches were done in PubMed Central, EMBASE, MEDLINE, SCOPUS and Cochrane library until December 2022. Meta-analysis was carried out using random-effects model. With 95% confidence intervals (CIs), pooled sensitivity and specificity were reported., Results: Twenty-six studies met the inclusion criteria. The pooled sensitivity of PET/CT was 89% (95% CI 84-93%), while the pooled specificity was 86% (95% CI 79-91%). The AUROC was 0.94 (95% CI 0.72-0.99). There was statistically significant heterogeneity (p < 0.001) with I2 value of 96%. The diagnostic odds ratio was 52 (95% CI 26-106). Likelihood ratio positive was 6.5 (95% CI 4.1-10.3) and negative was 0.13 (95% CI 0.08-0.19)., Conclusion: Our study found that PET/CT was found to have higher level of accuracy in terms of sensitivity and specificity. Further large-scale research can help to find answers for such questions and provide final conclusive evidence on the inclusion of the imaging modality into the routine clinical practice guidelines for suspected periprosthetic joint infection patients., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Soil microorganisms could obtain energy and nutrients during litter decomposition with the help of soil extracellular enzymes. The litter types were among the most critical factors that affect soil extracellular enzyme activities. However, how litter types modulate the soil extracellular enzyme activity with grassland gradation is unclear. Here, we conducted a 240-day experiment of two different types of litter decomposition on soil extracellular enzyme activity and stoichiometry in different degraded grasslands. We found that C-acquiring enzyme activity and the enzyme stoichiometry of C/N were higher in Chloris virgata litter than in Leymus chinensis litter at lightly degraded level and C-acquiring enzyme activity in C. virgata was 16.96% higher than in L. chinensis . P-acquiring enzyme activity had the same trend with litter types in moderately and highly degraded levels and it was 20.71% and 30.89% higher in C. virgata than that in L. chinensis , respectively. The change of the enzyme stoichiometry with litter types was only showed in the enzyme stoichiometry of C/N at lightly degraded level, suggesting that litter types only affected the microbial C limitation in lightly degraded grassland. Almost all soil extracellular enzyme activities and extracellular enzyme stoichiometry, except the enzyme stoichiometry of N/P, decreased with grassland degraded level increasing. All vector angles were less than 45° suggesting that soil microorganisms were limited by N rather than by P during the decomposition process. Enzyme vector analysis revealed that soil microbial communities were co-limited by C and N during litter decomposition. Moreover, based on Random Forest (explaining more than 80%), we found that soil total nitrogen, total carbon, total phosphorus, dissolved organic C, pH and EC were important factors affecting soil enzyme activities by degradation levels. Our results emphasized that degradation levels could modulate the influences of litter types on soil extracellular enzyme activity. Our study enhanced our understanding in resource requirements for microbial communities to litter resources in degraded grassland and helped us to provide new ideas for improving degraded grassland ecosystems., 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 Li, Niu, Wang, Yang, Liu, Wu and Guan.)

Aprepitant has been classified into BCS class IV, which has low permeability and poor water solubility, resulting in low bioavailability. This study focused on improving its permeability and solubility in order to improve the oral bioavailability of aprepitant. Hydroxypropyl chitosan (HPCS) was used as a stabilizer for the nanosuspension and wet milling was utilized for improving aprepitant's bioavailability and solubility. The resulting nanosuspension size was 151 ± 14.5 nm and its zeta potential was 63.5 ± 0.34 Mv. The spectral characteristics (XRPD, DSC, TEM) of the nanosuspension suggested that aprepitant existed in the crystalline form and that nanosuspension had 2-fold higher solubility than aprepitant. Hydroxypropyl chitosan can significantly reduce the TEER of Caco-2 cells and the P app of the suspension in Caco-2 cells increased by 2.2 times compared with aprepitant. The relative bioavailability of the nanosuspension was 147.7% compared with the commercial capsule., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

This study focused on improving the physicochemical characteristics of aprepitant with poor water solubility by preparing solid dispersion (SD). To prepare the SD with HPMCAS-LF, the solvent evaporation method was applied. Based on dissolution analysis, the dissolution rate of SD increased by five times compared with aprepitant. In addition, scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC) results suggested the presence of amorphous-form aprepitant inside SD. According to Fourier transform infrared (FTIR) spectroscopy, intermolecular hydrogen bonds were detected between polymer and aprepitant. The Caco-2 cell experiment proved that SD did not lower the transepithelial electrical resistance (TEER) values but improved the permeation amount of aprepitant. Additionally, the SD of aprepitant displayed excellent stability., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Roll-to-roll (R2R) imprinting is a high-throughput and low-cost continuous manufacturing technique for the mass production of high-quality functional optical polymer films. In fabricating optical films, roll molds with high precision and surface finishs are key tooling components in the R2R imprinting process. However, the trimmed radial Fresnel array results in discontinuity of the machining trajectory. Therefore, direct diamond turning of trimmed radial Fresnel array on a roller mold was considered infeasible. We use the diamond microscraping method to manufacture the trimmed radial Fresnel array on the roller mold. The trimmed radial Fresnel array is divided into trimmed and the complete Fresnel structure to be machined separately. The trimmed part adopts the rounded corners method to avoid a damage machined surface. Due to the large size and heavy weight of the roller mold, conventional offline measurement methods cannot be used, so we measure and evaluate its cross-sectional profile by an on-machine measurement method to verify the feasibility of the proposed method. We provide a solution for surface machining of discontinuous and complex microstructures on the roller mold.

Tropospheric attenuations can be significant in the millimeter wave (mmWave) frequency bands; hence, accurate prediction modeling of tropospheric attenuation is important for reliable mmWave communication. Several models have been established by the International Telecommunication Union (ITU), yet estimation accuracy is limited due to the large spatial scales used for model input parameters. In this paper, we address this and apply local precipitation data to analyze tropospheric attenuation statistics and compare to results when using ITU regional input rain data. Specifically, tropospheric attenuation is predicted via simulations using the ITU method at 30, 60, and 90 GHz in four distinct geographic locations with different climate types. From our simulations, we gather statistics for annual average rain attenuation, worst month rain attenuation, and rain attenuation per decade. Our results indicate that when using local measured rain data, for 1 km link distance, mean rain event attenuation increases from 0.5 to 2 dB. Local rain data yield larger attenuations at essentially all percentages of time not exceeded (essentially corresponding to all probability values): for example, for 0.1% of time not exceeded, in Columbia, SC, rain attenuation for 30 GHz frequency increases to 9 dB with local rain data, compared to 5 dB with ITU's regional data, corresponding to rain rates of 38.2 and 17.5 mm/h, respectively; at the same probability and location, the 90 GHz attenuation increases by 10 dB, from 10 to 20 dB when local rain data are used. Fog attenuations are also appreciable, reaching 8 dB for the 90 GHz frequency. Moreover, for the example locations, peak rain attenuations have increased at a rate of approximately 2 dB/decade over the past 50 years. Our results indicate that actual tropospheric attenuations may be substantially larger than that predicted by the ITU model when using regional rain rate data., (© 2022 The Authors. International Journal of Communication Systems published by John Wiley & Sons Ltd.)

The suspended particulate matter (SPM) is an important carrier of heavy metals transportation from land to sea, so it is significant to study the heavy metal pollution in SPM. The distribution and assessment of five heavy metals (Mn, Cr, Ni, Cu, and Pb) in SPM collected from Passur River and its estuary in Sundarban were studied in combination with water temperature, salinity, and turbidity. The results show that the heavy metal content and distribution in SPM are mainly controlled by runoff input, hydrodynamic process and the interaction process of salt and fresh water in estuaries. The quality evaluation results of heavy metals in SPM show that pollution degree is light. Studies on the heavy metals in SPM are of great significance to comprehensively evaluate regional pollution status and carry out early warning., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: In stent restenosis (ISR) is one of the major complications after stent implantation. Thus, there is a growing interest in identifying a biomarker for the onset of ISR. High levels of serum homocysteine (Hcy) have been associated with the progression of cardiovascular disease. Therefore, the study was carried out to quantify the correlation between serum Hcy and ISR severity. Compared with coronary angiography (CAG), Hcy levels provided a significantly better clinical detection of ISR severity after PCI. Methods: A total of 155 patients were recruited from Shanxi Bethune hospital, from 6 months to 2 years post PCI. Serum Hcy levels and postoperative angiography results were used to differentiate the patients into two experimental groups: ISR (>50% diametrical stenosis), and non-ISR. The non-ISR included two subgroups: intimal hyperplasia (10-50% diametrical stenosis), and recovery (<10% diametrical stenosis). In addition, a group of 80 healthy individuals was used as a negative control. The correlation between homocysteine level and ISR severity t was analyzed for all groups. In addition, the correlation between serum Hcy level and the severity of ISR in the experimental group was analyzed by the Pearson correlation test. Results: The serum Hcy level in the experimental group and control group was determined to be (20.21 ± 11.42) μmol/L and (15.11 ± 10.25) μmol/L respectively. The level of serum Hcy in the experimental group was significantly higher than in the control group ( t -value of 2.385; p -value of 0.019). The serum Hcy level in the restenosis and the intimal hyperplasia group was (25.72 ± 13.71) μmol/L and (17.35 ± 7.70) μmol/L respectively. The serum Hcy level in the restenosis group was significantly higher than in the intimal hyperplasia group ( t -value of 2.215; p -value of 0.033). The level of serum Hcy in the group without a plaque in the stent was (16.30 ± 6.08) μmol/L, whereas in the control group was (15.11 ± 10.25) μmol/L. The no plaque group had a slightly higher serum Hcy level than the control group ( t -value of 0.634; p- value of 0.528). All included patients were divided into four quartiles based on the serum Hcy concentration: quartile 1 (8.90-13.20 μmol/L), quartile 2 (13.30-16.45 μmol/L), quartile 3 (16.60-24.25 μmol/L) and quartile 4 (24.30-65.30 μ mol/L). The incidence of ISR was 5, 6.25, 7.5 and 15%, in the 1,2,3 and four quartiles respectively. The serum Hcy level in the experimental group was (20.21 ± 11.42) μmol/L, the severity of in-stent restenosis was (0.25 ± 0.31), ( R- value was 0.234; p- value was 0.037), indicating a correlation between serum Hcy and the severity of restenosis ( p < 0.05). Taking coronary angiography as the gold standard, a ROC curve analysis was performed on the serum Hcy levels for the experimental group. The area under the curve (AUC) was 0.718 (95% CI 0.585-0.854, p < 0.001), indicating that the serum Hcy concentration could predict ISR. On the ROC curve, the best critical value of serum Hcy concentration for predicting ISR was 20.05 μmol/L, with a sensitivity of 45% and specificity of 88.1%. Conclusion: A positive correlation was observed between homocysteine and the severity of restenosis after PCI, The level of Hcy could serve as a predictive biomarker for the severity of ISR., 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 Guo, Gao, Ahmed, Dong, Gao, Gong, Liu, Mao, Yue, Zheng, Li, Rong, Zhou, An, Gu and Zhang.)

Extracellular vesicles (EVs) are vesicular bodies (40-1000 nm) with double-layer membrane structures released by different cell types into extracellular environments, including apoptosis bodies, microvesicles, and exosomes. Exosomes (30-100 nm) are vesicles enclosed by extracellular membrane and contain effective molecules of secretory cells. They are derived from intracellular multivesicular bodies (MVBs) that fuse with the plasma membrane and release their intracellular vesicles by exocytosis. Research has shown that almost all human cells could secrete exosomes, which have a certain relationship with corresponding diseases. In chronic liver diseases, exosomes release a variety of bioactive components into extracellular spaces, mediating intercellular signal transduction and materials transport. Moreover, exosomes play a role in the diagnosis, treatment, and prognosis of various chronic liver diseases as potential biomarkers and therapeutic targets. Previous studies have found that mesenchymal stem cell-derived exosomes (MSC-ex) could alleviate acute and chronic liver injury and have the advantages of high biocompatibility and low immunogenicity. In this paper, we briefly summarize the role of exosomes in the pathogenesis of different chronic liver diseases and the latest research progresses of MSC-ex as the clinical therapeutic targets., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Chen Wang et al.)

Activated hepatic stellate cells (HSCs) are significant in liver fibrosis. Our past investigations have shown that human umbilical cord mesenchymal stem cells (hucMSCs) and their secreted exosomes (MSC-ex) could alleviate liver fibrosis via restraining HSCs activation. However, the mechanisms underlying the efficacy were not clear. Ferroptosis is a regulatory cell death caused by excessive lipid peroxidation, and it plays a vital role in the occurrence and development of liver fibrosis. In the present study, we aimed to study the proferroptosis effect and mechanism of MSC-ex in HSCs. MSC-ex were collected and purified from human umbilical cord MSCs. Proferroptosis effect of MSC-ex was examined in HSCs line LX-2 and CCl4 induced liver fibrosis in mice. Gene knockdown or overexpression approaches were used to investigate the biofactors in MSC-ex-mediated ferroptosis regulation. Results: MSC-ex could trigger HSCs ferroptosis by promoting ferroptosis-like cell death, ROS formation, mitochondrial dysfunction, Fe 2 + release, and lipid peroxidation in human HSCs line LX-2. Glutathione peroxidase 4 (GPX4) is a crucial regulator of ferroptosis. We found that intravenous injection of MSC-ex significantly decreased glutathione peroxidase 4 (GPX4) expression in activated HSCs and collagen deposition in experimental mouse fibrotic livers. Mechanistically, MSC-ex derived BECN1 promoted HSCs ferroptosis by suppressing xCT-driven GPX4 expression. In addition, ferritinophagy and necroptosis might also play a role in MSC-ex-promoted LX-2 cell death. Knockdown of BECN1 in MSC diminished proferroptosis and anti-fibrosis effects of MSC-ex in LX-2 and fibrotic livers. MSC-ex may promote xCT/GPX4 mediated HSCs ferroptosis through the delivery of BECN1 and highlights BECN1 as a potential biofactor for alleviating liver fibrosis., (© 2022. The Author(s).)

Background: Coronary angiography (CAG) is "gold standard" for the diagnosis of coronary heart disease (CHD). This study aimed to explore the diagnostic value of cardiopulmonary exercise testing (CPET) and the oxygen uptake kinetics indexes of CPET., Methods: One hundred thirty-one patients with chest pain who underwent coronary angiography in the Department of Cardiology of our hospital from April to September 2021 were selected. According to the results of angiography, the patients were divided into an observation group (patients with coronary heart disease, n=80) and a control group (patients without coronary heart disease, n=75). Both groups underwent CPET before angiography. The differences of peak oxygen uptake, anaerobic threshold, peak kilogram oxygen uptake, peak oxygen pulse, maximum exercise load, maximum metabolic equivalent, and exercise time between the two groups were compared. Also, the correlation between the above indexes and the degree of coronary artery stenosis was analyzed, and the clinical value of the CPET in the diagnosis of CHD was evaluated., Results: The peak oxygen uptake, anaerobic threshold, peak kilogram oxygen uptake, peak oxygen pulse, maximum exercise load, maximum metabolic equivalent, and exercise time in the observation group were lower than those in the control group (P<0.01), and were negatively correlated with the Gensini score (P<0.01). The area under the receiver operating characteristic (ROC) curve of the above seven indexes in the combined diagnosis of CHD was 0.974, the sensitivity was 86.40%, and the specificity was 98.50%, which was better than the clinical value of any of the above indexes alone., Conclusions: CPET is an effective non-invasive examination in the diagnosis of CHD, and has a certain clinical value in the evaluation of the severity of coronary artery stenosis., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-24/coif). The authors have no conflicts of interest to declare., (2022 Journal of Thoracic Disease. All rights reserved.)

The underlying mechanisms of human umbilical cord mesenchymal stem cells (hucMSCs) and their exosomes (hucMSC-Exs), which play significant roles in skin wound healing, remain poorly understood. By using a rat model of deep second-degree burn injury, the roles of hucMSC-Exs in angiogenesis and cutaneous wound healing in vivo were investigated. We found that hucMSC-Exs accelerated skin wound healing and angiogenesis, inducing a higher wound-closure rate and increased expression of CD31 in vivo. We also discovered that hucMSC-Exs contained angiopoietin-2 (Ang-2), and treatment with hucMSC-Exs enhanced the expression of the Ang-2 protein in the wound area and human umbilical vein endothelial cells (HUVECs) through exosomal-mediated Ang-2 transfer. Moreover, hucMSC-Exs promoted the proliferative, migratory, and tube-forming ability of HUVECs. Furthermore, overexpression of Ang-2 in hucMSC-Exs further enhanced HUVEC migration and tube formation and exerted therapeutic and proangiogenic effects in cutaneous wounds in rats, whereas knockdown of Ang-2 in hucMSC-Exs abrogated these therapeutic and proangiogenic effects. Taken together, our results indicated that hucMSC-Ex-derived Ang-2 plays a significant role in tube formation of HUVECs and promotion of angiogenesis, and further suggested that hucMSC-Ex-based therapy may serve as a promising therapeutic approach for promoting cutaneous wound healing.

Objective: To comprehensively analyze the global N 6 -methyladenosine (m 6 A) modification pattern in ameloblastoma., Methods: m 6 A peaks in ameloblastoma and normal oral tissues were detected by MeRIP-seq. Differentially methylated m 6 A sites within messenger RNAs (mRNAs), long no-coding RNA (lncRNAs) and circular RNA (circRNAs) were identified, followed by functional enrichment analysis. By comprehensively analyzing MeRIP-seq and RNA-seq data, differentially expressed mRNAs, lncRNAs and circRNAs containing differentially methylated sites were identified. RNA binding proteins (RBPs) were then identified for differentially methylated m 6 A sites., Results: In total, 3,673 differentially methylated m 6 A sites within coding genes were detected, of which 16.2% (704/3,673) were significantly upmethylated sites in ameloblastoma compared to normal oral tissues. Furthermore, 4,975 differentially methylated m 6 A sites within lncRNAs were identified, of which 29.4% (1,465/4,975) were upmethylated sites in ameloblastoma. We also found 364 differentially methylated m 6 A sites within circRNAs, of which 22.5% (82/364) were upmethylated sites in ameloblastoma. Differentially methylated m 6 A was most often harbored in the CDS (54.10%), followed by 5'UTR (21.71%). Functional enrichment analysis revealed that m 6 A modification could be involved in the development of ameloblastoma by organism developmental processes. A total of 158 RBPs within differentially methylated m 6 A sites were identified, which were significantly involved in mRNA metabolic process, mRNA processing, RNA processing, RNA splicing and RNA transport., Conclusion: Our findings for the first time provide m 6 A landscape of human ameloblastoma, which expand the understanding of m 6 A modifications and uncover regulation of lncRNAs and circRNAs through m 6 A modification in ameloblastoma., (Copyright © 2020 Niu, Xu, Liu, Chen, Qiao and Zhong.)

Herein, novel V-modified titania nanorod-aggregates (VTNA), consisting of fine individual nanorods in radial direction, were fabricated via an efficient microwave-assisted hydrothermal (MWH) route. VTNA with high crystallinity and homogeneous mesopores were obtained by 30 min MWH processing at 190 °C; moreover, a mixed rutile-anatase phase appeared after vanadium doping. XPS analysis revealed that vanadium existed in the forms of V 4+ and V 5+ on the surface of MWV05 with V 5+ being the dominant component, the content of which was approximately 3.5 times that of V 4+ . Vanadium implanting was achieved efficiently by doping 0.5 and 1 at% V using a rapid MWH process and contributed towards the dramatic improvement of the visible-light response, with E g decreasing from 2.91 to 2.71 and 2.57 eV with the increasing V doping content. MWV05 exhibited optimal photocatalytic degradation activity of water-soluble PCP-Na under solar light irradiation. The enhanced photodecomposition was attributed to the red-shift in the TiO 2 band-gap caused by vanadium impregnation, efficient charge separation due to the V 4+ /V 5+ synergistic effects and the free migration of charge carriers along the radial direction of the nanorods arranged in a self-assembled VTNA microstructure., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objective: To evaluate the effectiveness and safety of cervical spondylosis formula granules in reducing the symptoms of patients with the nerve root type and the vertebral artery type of cervical spondylosis., Methods: This was a multicenter, single-blind, randomized, controlled trial. From April 2002 to November 2003, 499 patients were randomly assigned to either the treatment or the control group. The treatment group was orally administered granules prepared with a formula for cervical spondylosis, while the control group was given Jingfukang granules. The treatment course was 1 month for both groups., Results: In patients with the nerve root type of cervical spondylosis, the total effect rate in the treatment group (87.21% ) was significantly higher than that in the control group (80.70%, P < 0.01). After the treatment period in both groups, the treatment group had a significantly greater rate of resolution of pain, numbness of the upper limbs, muscle strength of the upper limbs, and fatigue than the control group (all P < 0.05). In patients with the vertebral artery type of cervical spondylosis, the total effect rate in the treatment group (82.07%) was similar to that in the control group (71.21% , P > 0.05). After the treatment period in both groups, the treatment group had a significantly greater rate of resolution of weakness of the waist and knees than the control group (P < 0.05)., Conclusion: The cervical spondylosis formula granules significantly improve numbness, muscle strength, and fatigue, and reduce pain in patients with the nerve root type of cervical spondylosis, and improve the weakness of the waist and knees in patients with the vertebral artery type of cervical spondylosis.

Liver cancer cells can be reprogrammed into induced cancer stem cells (iCSCs) by exogenous expression of the reprogramming transcription factors Oct4, Sox2, Klf4 and c-Myc (OSKM). The nucleosome remodeling and deacetylase (NuRD) complex is essential for reprogramming somatic cells. In this study, we investigated the function of NuRD in the induction of liver CSCs. We showed that suppression of methyl-CpG binding domain protein 3 (MBD3), a core subunit of the NuRD repressor complex, together with OSKM transduction, induces conversion of liver cancer cells into stem-like cells. Expression of the transcription factor c-JUN is increased in MBD3-depleted iCSCs, and c-JUN activates endogenous pluripotent genes and regulates iCSC-related genes. These results indicate that MBD3/NuRD inhibits the induction of iCSCs, while c-JUN facilitates the generation of CSC-like properties. The iCSC reprogramming approach devised here provides a novel platform for dissection of the disordered signaling in liver CSCs. In addition, our results indicate that c-JUN may serve as a potential target for liver cancer therapy.

Wood is derived from the secondary growth of tree stems. In this study, we investigated the global changes of protein abundance in Populus early stems using a proteomic approach. Morphological and histochemical analyses revealed three typical stages during Populus early stems, which were the primary growth stage, the transition stage from primary to secondary growth and the secondary growth stage. A total of 231 spots were differentially abundant during various growth stages of Populus early stems. During Populus early stem lignifications, 87 differential spots continuously increased, while 49 spots continuously decreased. These two categories encompass 58.9% of all differential spots, which suggests significant molecular changes from primary to secondary growth. Among 231 spots, 165 unique proteins were identified using LC-ESI-Q-TOF-MS, which were classified into 14 biological function groups. The proteomic characteristics indicated that carbohydrate metabolism, oxido-reduction, protein degradation and secondary cell wall metabolism were the dominantly occurring biochemical processes during Populus early stem development. This study helps in elucidating biochemical processes and identifies potential wood formation-related proteins during tree early stem development. It is a comprehensive proteomic investigation on tree early stem development that, for the first time, reveals the overall molecular networks that occur during Populus early stem lignifications., (Copyright © 2015. Published by Elsevier B.V.)

Maturation of chloroplast ribosomal RNAs (rRNAs) comprises several endoribonucleolytic and exoribonucleolytic processing steps. However, little is known about the specific enzymes involved and the cleavage steps they catalyze. Here, we report the functional characterization of the single Arabidopsis (Arabidopsis thaliana) gene encoding a putative YbeY endoribonuclease. AtYbeY null mutants are seedling lethal, indicating that AtYbeY function is essential for plant growth. Knockdown plants display slow growth and show pale-green leaves. Physiological and ultrastructural analyses of atybeY mutants revealed impaired photosynthesis and defective chloroplast development. Fluorescent microcopy analysis showed that, when fused with the green fluorescence protein, AtYbeY is localized in chloroplasts. Immunoblot and RNA gel-blot assays revealed that the levels of chloroplast-encoded subunits of photosynthetic complexes are reduced in atybeY mutants, but the corresponding transcripts accumulate normally. In addition, atybeY mutants display defective maturation of both the 5' and 3' ends of 16S, 23S, and 4.5S rRNAs as well as decreased accumulation of mature transcripts from the transfer RNA genes contained in the chloroplast rRNA operon. Consequently, mutant plants show a severe deficiency in ribosome biogenesis, which, in turn, results in impaired plastid translational activity. Furthermore, biochemical assays show that recombinant AtYbeY is able to cleave chloroplast rRNAs as well as messenger RNAs and transfer RNAs in vitro. Taken together, our findings indicate that AtYbeY is a chloroplast-localized endoribonuclease that is required for chloroplast rRNA processing and thus for normal growth and development., (© 2015 American Society of Plant Biologists. All Rights Reserved.)

7-Ethyl-10-hydroxycamptothecin (SN38), an active metabolite of irinotecan (CPT-11), is a remarkably potent antitumor agent. The clinical application of SN38 has been extremely restricted by its insolubility in water. In this study, we successfully synthesized two macromolecular prodrugs of SN38 with different conjugate positions (chitosan-(C10-OH)SN38 and chitosan-(C20-OH)SN38) to improve the water solubility and antitumor activity of SN38. These prodrugs can self-assemble into micelles in aqueous medium. The particle size, morphology, zeta potential, and in vitro drug release of SN38 and its derivatives, as well as their cytotoxicity, pharmacokinetics, and in vivo antitumor activity in a xenograft BALB/c mouse model were studied. In vitro, chitosan-(C10-OH)SN38 (CS-(10s)SN38) and chitosan-(C20-OH) SN38 (CS-(20s)SN38) were 13.3- and 25.9-fold more potent than CPT-11 in the murine colon adenocarcinoma cell line CT26, respectively. The area under the curve (AUC)0-24 of SN38 after intravenously administering CS-(10s)SN38 and CS-(20s)SN38 to Sprague Dawley rats was greatly improved when compared with CPT-11 (both P<0.01). A larger AUC0-24 of CS-(20s)SN38 was observed when compared to CS-(10s)SN38 (P<0.05). Both of the novel self-assembled chitosan-SN38 prodrugs demonstrated superior anticancer activity to CPT-11 in the CT26 xenograft BALB/c mouse model. We have also investigated the differences between these macromolecular prodrug micelles with regards to enhancing the antitumor activity of SN38. CS-(20s)SN38 exhibited better in vivo antitumor activity than CS-(10s)SN38 at a dose of 2.5 mg/kg (P<0.05). In conclusion, both macromolecular prodrug micelles improved the in vivo conversion rate and antitumor activity of SN38, but the prodrug in which C20-OH was conjugated to macromolecular materials could be a more promising platform for SN38 delivery.

As an economic crop, pepper satisfies people's spicy taste and has medicinal uses worldwide. To gain a better understanding of Capsicum evolution, domestication, and specialization, we present here the genome sequence of the cultivated pepper Zunla-1 (C. annuum L.) and its wild progenitor Chiltepin (C. annuum var. glabriusculum). We estimate that the pepper genome expanded ∼0.3 Mya (with respect to the genome of other Solanaceae) by a rapid amplification of retrotransposons elements, resulting in a genome comprised of ∼81% repetitive sequences. Approximately 79% of 3.48-Gb scaffolds containing 34,476 protein-coding genes were anchored to chromosomes by a high-density genetic map. Comparison of cultivated and wild pepper genomes with 20 resequencing accessions revealed molecular footprints of artificial selection, providing us with a list of candidate domestication genes. We also found that dosage compensation effect of tandem duplication genes probably contributed to the pungent diversification in pepper. The Capsicum reference genome provides crucial information for the study of not only the evolution of the pepper genome but also, the Solanaceae family, and it will facilitate the establishment of more effective pepper breeding programs.

Background/aims: To investigate the expression profile of DJ-1 gene and its clinical relevance and prognostic value in hepatocellular carcinoma (HCC)., Methodology: Specimens from 149 HCC patients were applied for DJ-1 expression through immunohistochemistry. The correlation of DJ-1 levels with clinicopathologic variables and prognosis was analyzed. 32 paired HCC and para-carcinomatous liver tissue (PCLT) specimens from 149 HCC patients plus 10 hepatic cirrhosis specimens and 10 normal liver specimens were detected by semi-quantitative polymerase chain reaction (PCR) and Western blot., Results: DJ-1 was up-regulated significantly in HCC by semi-quantitative PCR and Western blot. DJ-1 expression closely correlated with preoperative AFP, liver cirrhosis, vein invasion, differentiation and Edmondson grade in HCCs by Pearson Chi-square test. Both of tumor-free survival time and overall survival time in the DJ-1 high expression group were shorter than those in the low expression group. DJ-1 was adopted as an independent prognostic factor for overall survival of HCC patients through multivariate Cox proportional hazard model analysis (HR, 2.568; p = 0.003). Additionally, immunohistochemistry analysis revealed that expression of DJ-1 negatively correlated with expression of tumor suppressor gene phosphatase and tensin homolog deleted on chromosome ten (PTEN) in HCC (r = -0.836; p < 0.001)., Conclusions: DJ-1 expression is significantly upregulated in HCC, and its expression level correlates with clinicopathological variables and prognosis of HCC patients, which suggests that DJ-1 maybe a candidate prognostic biomarker of HCC.

To investigate the difference in expression of hTERT gene between HbsAg-positive human hepatocellular carcinoma (HCC) and HbsAg-negative HCC and to explore the relationship between HBV infection and hTERT gene expression in HCC. The expression of hTERT protein in 30 cases of HbsAg positive HCC and 17 cases of HbsAg negative HCC was detected by immunohistochemistry (SP method), and the expression of hTERT mRNA was analyzed by reverse transcription polymerase chain reaction (RT-PCR). t-test, Chi-squared test and cochran- armitage trend test were used to see whether there was an interrelation between HBsAg and hTERT gene in HCC. The expression of hTERT protein was mostly located in plasm and occasionally in the nucleus of liver cancer cells. The positive rate of hTERT protein and hTERT mRNA in HbsAg positive HCC- 93.33% (28/30) and 83.33% (25/30) respectively which were much higher than those in HbsAg negative HCC- 52.94% (9/17), 47.06% (8/17) (P<0.01) respectively. HbsAg is related to hTERT gene expression in human hepatocellular carcinoma. The hTERT gene activated by the efficacious ingredient of HBV may play an important role in hepatocellular transformation and carcinogenesis.