Idebenone Exerts anti-Triple Negative Breast Cancer Effects via Dual Signaling Pathways of GADD45 and AMPK.

Idebenone, a mitochondrial regulator, has exhibited anti-cancer activity in neurogenic and prostate tumor cells; however, its efficacy and specific targets in the treatment of triple-negative breast cancer (TNBC) remain unclear. This study aims to evaluate the potential of Idebenone as a therapeutic agent for TNBC. TNBC cell lines and Xenograft mouse models were used to assess the effect of Idebenone on TNBC both in vitro and in vivo. To investigate the underlying mechanism of Idebenone's effect on TNBC, cell viability assay, transwell invasion assay, cell cycle analysis, apoptosis assay, mitochondrial membrane potential assay, immunofluorescence staining, and transcriptome sequencing were utilized. The results showed that Idebenone impeded the proliferation, colony formation, migration, and invasion of TNBC cells, suppressed apoptosis, and halted the cell cycle in the G2/M phase. The inhibitory effect of Idebenone on TNBC was associated with the GADD45/CyclinB/CDK1 signaling pathway. By disrupting the mitochondrial membrane potential (MMP) and promoting mitophagy, Idebenone promoted cell autophagy through the AMPK/mTOR pathway, thus further suppressing the proliferation of TNBC cells. Furthermore, we found that Idebenone inhibited the development of TNBC in vivo. In conclusion, Idebenone may be a promising therapeutic option for TNBC as it is capable of inducing autophagy and apoptosis.

Feasibility and solidification mechanism study of self-sustaining smoldering remediation for copper and lead-contaminated soil.

Soil heavy metal pollution is an important issue that affects human health and ecological well-being. In-situ thermal treatment techniques, such as self-sustaining smoldering combustion (SSS), have been widely studied for the treatment of organic pollutants. However, the lack of fuel in heavy metal-contaminated soil has hindered its application. In this study, we used corn straw as fuel to investigate the feasibility of SSS remediation for copper and lead in heavy metal-contaminated soil, as well as to explore the remediation mechanism. The results of the study showed that SSS increased soil pH, electrical conductivity (EC), total phosphorus (TP), total potassium (TK), rapidly available phosphorus (AP), and available potassium (AK), while decreasing total nitrogen (TN), alkali-hydrolyzed nitrogen (AN), and cation exchange capacity (CEC). The oxidation state of copper (Cu) increased from 10% to 21%-40%, and the residual state of lead (Pb) increased from 18% to 51%-73%. The Toxicity characteristic leaching procedure (TCLP) of Cu decreased by a maximum of 81.08%, and the extracted state of Diethylenetriaminepentaacetic acid (DTPA) decreased by 67.63%; the TCLP of Pb decreased by a maximum of 81.87%, and DTPA decreased by a maximum of 85.68%. The study indicates that SSS using corn straw as fuel successfully achieved remediation of heavy metal-contaminated soil. However, SSS does not reduce the content of copper and lead; it only changes their forms in the soil. The main reasons for the fixation of copper and lead during the SSS process are the adsorption of biochar, complexation with -OH functional groups, binding with π electrons, and the formation of crystalline compounds. This research provides a reference for the application of SSS in heavy metal-contaminated soil and has potential practical implications.

Interactions between inhalable aged microplastics and lung surfactant: Potential pulmonary health risks.

The relationship between microplastics (MPs) and human respiratory health has garnered significant attention since inhalation constitutes the primary pathway for atmospheric MP exposure. While recent studies have revealed respiratory risks associated with MPs, virgin MPs used as plastic surrogates in these experiments did not represent the MPs that occur naturally and that undergo aging effects. Thus, the effects of aged MPs on respiratory health remain unknown. We herein analyzed the interaction between inhalable aged MPs with lung surfactant (LS) extracted from porcine lungs vis-à-vis interfacial chemistry employing in-vitro experiments, and explored oxidative damage induced by aged MPs in simulated lung fluid (SLF) and the underlying mechanisms of action. Our results showed that aged MPs significantly increased the surface tension of the LS, accompanied by a diminution in its foaming ability. The stronger adsorptive capacity of the aged MPs toward the phospholipids of LS appeared to produce increased surface tension, while the change in foaming ability might have resulted from a variation in the protein secondary structure and the adsorption of proteins onto MPs. The adsorption of phospholipid and protein components then led to the aggregation of MPs in SLF, where the aged MPs exhibited smaller hydrodynamic diameters in comparison with the unaged MPs, likely interacting with biomolecules in bodily fluids to exacerbate health hazards. Persistent free radicals were also formed on aged MPs, inducing the formation of reactive oxygen species such as superoxide radicals (O2•-), hydrogen peroxide (HOOH), and hydroxyl radicals (•OH); this would lead to LS lipid peroxidation and protein damage and increase the risk of respiratory disease. Our investigation was the first-ever to reveal a potential toxic effect of aged MPs and their actions on the human respiratory system, of great significance in understanding the risk of inhaled MPs on lung health.

Red mud with enhanced dealkalization performance by supercritical water technology for efficient SO2 capture.

The total de-alkalization treatment of industrial solid waste red mud (RM) has been a worldwide challenge. Removing the insoluble structural alkali fraction from RM is the key to enhancing the sustainable utilization of RM resources. In this paper, supercritical water (SCW) and leaching agents were used for the first time to de-alkalize the Bayer RM and to remove sulfur dioxide (SO2) from flue gas with the de-alkalized RM slurry. The results showed that the optimum alkali removal and Fe leaching rates of RM-CaO-SW slurry were 97.90 ± 0.88% and 82.70 ± 0.95%, respectively. Results confirmed that the SCW technique accelerated the disruption of (Al-O) and (Si-O) bonds and the structural disintegration of aluminosilicate minerals, facilitating the conversion of insoluble structural alkalis to soluble chemical alkalis. The exchangeable Ca2+ displaced Na+ in the remaining insoluble base, producing soluble sodium salts or alkalis. CaO consumed SiO2, which was tightly bound to Fe2O3 in RM, and released Fe2O3, which promoted Fe leaching. RM-SCW showed the best desulfurization performance, which maintained 88.99 ± 0.0020% at 450 min, followed by RM-CaO-SW (450 min, 60.75 ± 6.00%) and RM (180 min, 88.52% ± 0.00068). The neutralization of alkaline components, the redox of metal oxides, and the liquid-phase catalytic oxidation of Fe contributed to the excellent desulfurization performance of the RM-SCW slurry. A promising approach shown in this study is beneficial to RM waste use, SO2 pollution control, and sustainable growth of the aluminum industry.

[Expressions of NLRP1 and NLRC4 inflammasomes in prostate cancer and their clinical value].

OBJECTIVE: To explore the clinical value of the inflammasomes NLRP1 and NLRC4 in the diagnosis and treatment of PCa. METHODS: Using immunohistochemical staining, we detected the expressions of the inflammasomes NLRP1 and NLRC4 and the inflammatory cytokines IL-18 and IL-1ß in 54 cases of BPH and 58 cases of PCa treated in Pinghu First People's Hospital from January 2022 to May 2022. We analyzed the characteristics of their expressions in the two groups of patients and the correlation of NLRP1 and NLRC4 expressions with tPSA, fPSA and Gleason scores in the PCa patients. Based on the Cancer Genome Atlas dataset, we compared the expressions of NLRP1 and NLRC4 in different stages of PCa. RESULTS: The NLRP1 and NLRC4 expressions were significantly increased in the PCa patients (P < 0.001). The expression of NLRP1 was linearly correlated with those of IL-1ß and IL-18 (P < 0.05), and so was the expression of NLRC4 with that of IL-18 (P < 0.05). The expressions of NLRP1 and NLRC4 were positively correlated with the Gleason scores of the PCa patients (P < 0.05), the former remarkably higher in T3 and T4 than in T1 (P > 0.05), and the latter markedly higher in T2, T3 and T4 than in T1 (P < 0.05). CONCLUSION: The inflammasomes NLRP1 and NLRC4 are highly expressed in PCa and facilitate tumorgenesis by promoting the maturation and release of the inflammatory cytokines IL-1ß and IL-18, which indicates their important role in the progression of tumors and clinical value in the risk assessment and prognosis of PCa.

Study on Tailings Covering System Constructed by Geological Polymerization of Mine Waste. Part 2: Simulation of Oxidation Inhibition of Overburden on Acid-producing Tailings.

Acid mine drainage (AMD) is a well-recognized environmental issue associated with mining production worldwide. The second part of our study aims to assess the protective effect of using a polymer hard layer (PHL) by conducting sulphur-enriched tailing-based column experiments. An oxygen (O2) barrier was simulated using a designed column device filled with different types of tailings. All experimental columns underwent six drying-wetting cycles, and the chemical properties of the tailings and leachate were detected after every cycle. The permeability coefficient of the PHL was only 1.16 × 10- 5 cm/s. Over the entire experimental period, none of the leachates collected from column 4 using the PHL as an O2 barrier. Moreover, the level of redox potential and pH and the contents of heavy metals such as Cu and Zn were stable in PHL covering system. These results show that a PHL is the optimal covering system.

Study on the Role of Quartz in the Bio-Oxidation of Sulfide Minerals From Mine Solid Waste.

Sulfide-containing mine waste was oxidized to produce acid mine drainage, which lead to acidification of surrounding soil and downstream rivers and posed a threat to the surrounding environment. Quartz often coexists with sulfide minerals and affects the oxidation of sulfide minerals. In order to explore the role of quartz in the bio-oxidation of sulfide minerals in mine solid waste, the mixed minerals of quartz and sulfide minerals were bio-oxidized by Acidithiobacillus ferrooxidans. The results showed that quartz could improve the microbial activity and increase the acid production of sulfide minerals. The larger the proportion of quartz in bio-oxidation of sulfide minerals, the less the production of secondary minerals such as jarosite, and the larger the leaching amount of iron and sulfate. This research provides new ideas for speeding up the bio-oxidation of sulfide mineral to remove iron and sulfate. It provides a new way to solve acid pollution caused by oxidation of sulfide minerals.

Study on Tailings Covering System Constructed by Geological Polymerization of Mine Waste, Part 1: Material Characterization and Cover Construction.

Acid mine drainage (AMD) is a serious and persistent environmental pollution problem. At present, many studies have focused on the tailings pond's cover systems. This paper introduced the research results of using tin tailings from Laili mountain to make the covering layer of tailings pond. The first part included a detailed description of tailings characterization and acid production potential. On this basis, the hard layer (HL) was prepared and its feasibility as oxidation barrier was evaluated. It was found that when the proportion of tailings waste was 70%, the immobilization efficiency of heavy metals can reach more than 99.45%, and the pH of leaching solution was about 10.8. Moreover, the beneficial effect of solid waste addition on the HL was also verified. This suggests that HL as a post-mining restorative strategy has strong positive influence on pollution control.

Formation Process of Silicate-Iron Oxyhydroxide Complex and Its Influence on the Distribution of Heavy Metals in Mining Area.

Silicate-iron oxyhydroxide complex formed by mineral weathering has an important influence on the geochemical reactions of heavy metals in mining areas. In this work, tailings were collected from an abandoned iron tailings pond, and the physicochemical properties and distribution of heavy metals were studied under natural weathering and hydraulic processes. The results showed that Fe2+ in the iron tailings were transported to the surface during the weathering process, and then the iron oxyhydroxide formed by mineralization adsorbed Cu2+ and Zn2+. Silicic acid and exchangeable acid were released during the formation of binary agglomerates between hydroxy iron oxide and kaolin, then they migrated to the lower area of a tailing pond via surface runoff. Finally, silicate-iron oxyhydroxide complex were formed. The heavy metals were replaced by H+ and penetrated to the bottom layer with water. This research provides an important scientific basis for the prevention and control of heavy metal pollution in mining areas.

Anisotropic thermal analyses of a high efficiency Tm:YAP slab laser and its intra-cavity pumping for Ho lasers.

We evaluate the thermal effects of a c-cut Tm:YAP slab laser by considering the anisotropic properties of the biaxial YAP crystal. Significant improvements in thermal stress were demonstrated by selecting the crystallographic a-axis, which possesses higher thermal conductivity and thermal expansion, as the direction of the slab thickness. A maximum laser power of 30 W (E//a) at 2 µm was obtained under an incident LD power of 55 W with an optical conversion efficiency of 55.4% and slope efficiency of 61.8% using the a-slab. The slab laser was then used for realizing compact Ho lasers via intra-cavity pumping, resulting in a 0.8 W Ho:YAG laser and a 5.5 W Ho:YAP laser (E//b) at 2.12 µm and 2.13 µm, respectively.

Direct 800 nm diode-pumped Holmium laser with broad pump wavelength range and temperature adaptability.

We developed an 808 nm diode laser pumped composite Holmium laser via the integration of Tm-doped and Ho-doped YAG crystals into a single bulk structure. A maximum output power of 1.8 W at 2122 nm with near diffraction-limited beam quality was achieved for an absorbed pump power of approximately 7 W. Given that the pump wavelength is approximately 20 nm away from the absorption peak of the Tm-doped region of the crystal, pump wavelength adaptability of the Tm/Ho composite laser was effectively demonstrated. In this case, a pump range width in excess of 40 nm at approximately 800 nm was predicted by defining the pump spectrum of the gain medium. The temperature adaptability of the Ho laser was demonstrated by varying the cooling temperature from 9 °C to 27 °C. This resulted in Ho laser operation above 1.5 W with a power deviation below 10%. This work presents the experimental results for a compact assessable 2.1 µm laser without pump wavelength and operation temperature restrictions.

Manipulating the wavelength-drift of a Tm laser for resonance enhancement in an intra-cavity pumped Ho laser.

We demonstrate an enhancement mechanism and thermal model for intra-cavity pumped lasers, where resonance enhancement in intra-cavity pumped Ho laser was achieved by manipulating the wavelength-drift nature of the Tm laser for the first time. Optical conversion efficiency of 37.5% from an absorbed 785 nm diode laser to a Ho laser was obtained with a maximum output power of 7.51 W at 2122 nm, which is comparable to the conversion efficiency in 1.9 µm LD pumped Ho lasers. Meanwhile, more severe thermal effects in the Ho-doped gain medium than the Tm-doped one at high power operation were verified based on the built thermal model. This work benefits the design or evaluation of intra-cavity pumped lasers, and the resonance enhancement originated from the difference in reabsorption loss between stark levels at the lasing manifolds of quasi-three-level rare-earth ions has great interest to improve the existing intra-cavity pumped lasers or explore novel lasers.

2.1 µm composite Tm/Ho:YAG laser.

We realize Ho laser operation in a composite Tm/Ho:YAG gain medium for the first time, to the best of our knowledge, which was integrated via diffusion bonding the Tm-doped and Ho-doped crystals into a single bulk structure. A maximum output power around 6 W was obtained with a slope efficiency of 40.1% and conversion efficiency (CE) of 33.6% from the absorbed 785 nm laser diode to 2122 nm Ho laser, which is comparable with CE in 1.9 µm LD pumped Ho lasers. Such a scheme is demonstrated to be another valid way for Ho laser generation here, which is of significance to be adopted in other host media or waveguide structures for an assessable, compact, and efficient Ho laser.

Passively Q-switched solid-state Tm:YAG laser using topological insulator Bi2Te3 as a saturable absorber.

We demonstrated a passively Q-switched solid-state Tm:YAG laser using topological insulator (TI) Bi2Te3 as the saturable absorber (SA) for the first time, to the best of our knowledge. The Q-switched laser pulses were obtained with the minimum pulse width of 382 ns, the maximum pulse energy of 4.8 µJ, the maximum average output power of 272 mW, and a pulse repetition rate of 57.67 kHz. The results indicate that Bi2Te3 can be a promising kind of saturable absorber in the 2 µm wavelength region.

Efficient 2122 nm Ho:YAG laser intra-cavity pumped by a narrowband-diode-pumped Tm:YAG laser.

We first demonstrate an efficient Ho:YAG laser intra-cavity pumped by a narrowband-diode-pumped Tm:YAG laser. The pump wavelength of the laser diode was selected according to the excitation peak which is also one of the absorption peaks of a 3.5 at. % Tm:YAG crystal and was locked by volume Bragg gratings. In the Tm laser experiment, a maximum output power of 11.12 W, corresponding to a slope efficiency of 51.6%, was obtained. In the Ho laser experiment, a maximum output power of 8.03 W at 2122 nm with a slope efficiency of 38% was obtained for 24.96 W of diode pump power incident on the Tm:YAG rod.

[Efficacy of yindan xinnaotong soft capsule on cerebral infarction reconvalescents of static blood blocking collaterals syndrome: a randomized controlled study].

OBJECTIVE: To evaluate the efficacy and safety of Yindan Xinnaotong Soft Capsule (YXSC) on cerebral infarction (CI) reconvalescents of static blood blocking collaterals syndrome (SBBCS). METHODS: Totally 118 CI reconvalescents of SBBCS were randomly assigned to the test group (treated by YXSC) and the control group [treated by Naoxintong Capsule (NC)], 59 in each group. The therapeutic course for all was 12 weeks. Changes of National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), modified Rankin Scale (mRS), Chinese medical syndrome scores, and serum lipid indices were observed in the two groups. RESULTS: Compared with the control group, the patient proportion of improving activities of daily life by more than or equal to 75 score was elevated (80.7% vs 62.5%; P < 0.05). Compared with before treatment in the same group, the NIHSS score decreased at post-treatment 4, 8, and 12 weeks in the two groups (P < 0.05). The patient proportion of dropped NIHSS score by more than or equal to 5 score was lowered (80.7% vs 57.14%), and the total effective rate of improving Chinese medical syndromes was superior in the test group after 12-week treatment (89.47% vs 71.43%, all P < 0.05). After 12-week treatment there was no statistical difference in the patient proportion of lowering mRS lower than or equal to 2 or blood lipids between the two groups (P > 0.05). CONCLUSION: YXSC showed certain effect in improving activities of daily life, attenuating the neurological impairment, and elevating the total effective rate of improving Chinese medical syndromes in CI patients in the recovery stage.

Analysis of vacuum negative pressure therapy and traditional Chinese medicine lavage in combination with tadalafil for vascular erectile dysfunction.

This study investigates the clinical effects of the novel Traditional Chinese Medicine (TCM) topical wash used in combination with negative pressure irrigation and tadalafil for the treatment of vascular erectile dysfunction. Eighty-seven patients with vascular erectile dysfunction were divided into an observation group and a control group. The observation group was administered negative pressure irrigation (TCM) in combination with oral tadalafil for four weeks, and the control group was administered oral tadalafil for four weeks. The observation group included 21 patients with arterial erectile dysfunction and 22 with intravenous erectile dysfunction. After treatment, IIEF-5, EHS, GAD scores, PSV, EDV and RI in observation group were improved compared with those before treatment (P = 0.000, 0.000, 0.000, L0.000/R0.000, L0.000/R0.000, L0.003/R0.000). Erectile function (IIEF-5, EHS) was significantly improved compared with the control group (P = 0.008, 0.002). In the observation group, there were 21 cases of arterial erectile dysfunction and 22 cases of intravenous erectile dysfunction. After treatment, PSV of arterial ED improved significantly (P = L0.000/R0.000), but EDV did not decrease significantly (P = L0.084/R 0.098). In patients with venous ED, PSV increased (P = L0.026/R0.032) and EDV decreased significantly (P = L0.000/R0.000). These findings suggest that TCM negative pressure lavage combined with tadalafil improves the blood supply of the penile artery, relaxes smooth muscle, and improves the closing mechanism of venous vessels in patients with vascular erectile dysfunction, ultimately improving the erectile function.

Expression and clinical value of NLRP1 and NLRC4 inflammasomes in prostate cancer.

The present study explored the clinical value of the protein expression levels of nucleotide binding oligomerization-like receptor family pyrin domain containing 1 (NLRP1) and nucleotide-binding oligomerization domain leucine-rich repeat and caspase recruitment domain-containing 4 (NLRC4) inflammasomes in the diagnosis and treatment of prostate cancer. A total of 54 patients with prostatic hyperplasia and 58 patients with prostate cancer were recruited at The First People's Hospital of Pinghu between January and May 2022. Immunohistochemical staining was used to determine the protein expression levels of the NLRP1 and NLRC4 inflammasomes in addition to the proinflammatory cytokines IL-18 and IL-1ß in the two groups of patients. The protein expression levels of NLRP1 and NLRC4 inflammasome were significantly increased in patients with prostate cancer compared with patients with prostate hyperplasia. The differences in expression of NLRP1 and NLRC4 inflammatory vesicles in prostate cancer of different stages were also compared based on data from The Cancer Genome Atlas. The protein expression level of NLRP1 demonstrated a significant positive correlation with IL-1ß and IL-18 expression, and the protein expression level of the NLRC4 inflammasome was significantly positively correlated with IL-18 expression. The protein expression levels of both NLRP1 and NLRC4 demonstrated a significant positive correlation with the Gleason score of prostate cancer. The expression of NLRP1 in tumor (T)3/T4 was significantly higher compared with T1 and expression of the NLRC4 inflammasome in T2 and T3/T4 was significantly higher compared with T1. Expression of the NLRP1 and NLRC4 inflammasomes was significantly higher in patients with prostate cancer, compared with patients with prostatic hyperplasia. Therefore, expression of NLRP1 and NLRC4 may promote tumorigenesis by promoting the maturation and release of proinflammatory cytokines IL-1ß and IL-18. Expression of the NLRP1 and NLRC4 inflammasomes demonstrated a significant positive correlation with the risk of prostate cancer. Expression of the NLRP1 and NLRC4 inflammasomes in middle- and advanced-stage tumors was higher compared with early-stage tumors. These results suggested that inflammasome expression may serve a significant role in the progression of tumors and could provide a fixed value for the risk assessment and prognosis prediction of prostate cancer.

Remediation of Cr(VI)-contaminated soil using self-sustaining smoldering.

Self-sustaining smoldering is an emerging technology for nonaqueous-phase liquid remediation; however, it is rarely applied for Cr(VI)-contaminated soil treatment. In this study, self-sustaining smoldering using rice straw (RS) as a surrogate fuel was applied to remediate Cr(VI)-contaminated soil for the first time. Thirteen one-dimensional vertical smoldering experiments were conducted to investigate the effectiveness of the smoldering method and the effects of key experimental parameters on smoldering remediation performance. Smoldering was observed to be self-sustaining within the range of RS particle size from <0.16 to 2.00-4.00 mm, airflow from 0.2 to 1 m3/h, and Cr(VI)-impacted soil/RS ratios from 2:1 to 6:1. The Cr(VI)-contaminated soil was effectively remediated, which was confirmed by lowered Cr(VI) contents in the treated samples (decreased by 52.22-86.57%) and the elevated fraction of Cr oxidizable and residual form (increased by 1.14-3.30 and 2.97-4.00 times, respectively), compared to the control. The reducing gases (CO and CxHy) generated during the smoldering played a crucial role in the remediation process. The contents of available P and K in the remediated soil containing the remaining biochar and ash increased, thus improving soil reusability. Hence, this study shows that smoldering with RS as supplemental fuel is a promising Cr(VI)-contaminated soil management technique without supplying substantial external energy.

Interactions between CuO NPs and PS: The release of copper ions and oxidative damage.

Copper oxide nanoparticles (CuO NPs) can adversely affect lung health possibly by inducing oxidative damage through the release of copper ions. However, the migration and transformation processes of CuO NPs in lung lining fluid is still unclear, and there are still conflicting reports of redox reactions involving copper ions. To address this, we examined the release of copper ions from CuO NPs in simulated lung fluid supplemented with pulmonary surfactant (PS), and further analyzed the mechanisms of PS-CuO NPs interactions and the health hazards. The results showed that the phospholipid of PS was adsorbed on the particle surface, which not only induced aggregation of the particles but also provided a reaction environment for the interaction of PS with CuO NPs. PS was able to promote the release of ions from CuO NPs, of which the protein was a key component. Lipid peroxidation, protein destabilization, and disruption of the interfacial chemistry also occurred in the PS-CuO NPs interactions, during which copper ions were present only as divalent cations. Meanwhile, the contribution of the particle surface cannot be neglected in the oxidative damage to the lung caused by CuO NPs. Through reacting with biomolecules, CuO NPs accomplished ion release and induced oxidative damage associated with PS. This research was the first to reveal the mechanism of CuO NPs releasing copper ions and inducing lipid oxidative damage in the presence of PS, which provides a new idea of transition metal-induced health risk in human body.