Targeting SMYD2 promotes ferroptosis and impacts the progression of pancreatic cancer through the c-Myc/NCOA4 axis-mediated ferritinophagy.

BACKGROUND: Pancreatic cancer (PC) is characterized by a poor prognosis and limited treatment options. Ferroptosis plays an important role in cancer, SET and MYND domain-containing protein 2 (SMYD2) is widely expressed in various cancers. However, the role of SMYD2 in regulating ferroptosis in PC remains unexplored. This study aimed to investigate the role of SMYD2 in mediating ferroptosis and its mechanistic implications in PC progression. METHODS: The levels of SMYD2, c-Myc, and NCOA4 were assessed in PC tissues, and peritumoral tissues. SMYD2 expression was further analyzed in human PC cell lines. In BxPC3 cells, the expression of c-Myc, NCOA4, autophagy-related proteins, and mitochondrial morphology, was evaluated following transfection with si-SMYD2 and treatment with autophagy inhibitors and ferroptosis inhibitors. Ferroptosis levels were quantified using flow cytometry and ELISA assays. RNA immunoprecipitation was conducted to elucidate the interaction between c-Myc and NCOA4 mRNA. A xenograft mouse model was constructed to validate the impact of SMYD2 knockdown on PC growth. RESULTS: SMYD2 and c-Myc were found to be highly expressed in PC tissues, while NCOA4 showed reduced expression. Among the PC cell lines studied, BxPC3 cells exhibited the highest SMYD2 expression. SMYD2 knockdown led to decreased c-Myc levels, increased NCOA4 expression, reduced autophagy-related protein expression, mitochondrial shrinkage, and heightened ferroptosis levels. Additionally, an interaction between c-Myc and NCOA4 was identified. In vivo, SMYD2 knockdown inhibited tumor growth. CONCLUSIONS: Targeting SMYD2 inhibits PC progression by promoting ferritinophagy-dependent ferroptosis through the c-Myc/NCOA4 axis. These findings provide insights into potential diagnostic and therapeutic strategies for PC.

Astragaloside IV protects brain cells from ischemia-reperfusion injury by inhibiting ryanodine receptor expression and reducing the expression of P-Src and P-GRK2.

Astragaloside IV, a prime active component of Astragalus membranaceus, has potential as a neuroprotectant. We aimed to identify the active ingredients in A. membranaceus and assess if Astragaloside IV can improve cerebral ischemia-reperfusion injury (CIRI) cell apoptosis by reducing P-Src and P-GRK2 via ryanodine receptor (RyR) expression inhibition. We used bioinformatics analysis to examine the effects of A. membranaceus on ischemic stroke. We studied brain samples from middle cerebral artery occlusion (MCAO) mice treated with normal saline, Astragaloside IV, and sham mice for pathology and Western blot tests. We also tested PC12 cells in vitro with or without Astragaloside IV or GSK180736A using Western blotting and fluorescence assays. Our bioinformatics analysis suggested a possible association between A. membranaceus, calcium ion pathways, and apoptosis pathways. Western blot data indicated Astragaloside IV significantly decreased RyR, p-Src, and downstream phosphorylated GRK2, PLC, CaMKII, and IP3R levels in MCAO mice brains. Astragaloside IV also considerably inhibited pro-apoptotic and oxidative stress-associated proteins' expression while boosting anti-apoptotic protein expression. The results suggest Astragaloside IV can inhibit RyR expression, subsequently reducing brain cell apoptosis.

A novel dual-target Septin9 methylation assay for improved detection of early-stage colorectal cancer and high-grade intraepithelial neoplasia.

BACKGROUND: Colorectal cancer (CRC) ranks as the third most common malignancies in the world, and periodic examination of the patient is advantageous in reducing the mortality of CRC. The first blood-based Septin9 gene methylation assay which recognized by the US FDA for CRC examination was Epi proColon. However, this assay was not broadly applied in the current clinical guideline because of its relatively lower sensitivity in the detection of early-stage CRC. METHODS: This study aimed at developing a new multiplex Septin9 methylation assay (ColonUSK) which simultaneously evaluates two CpG-rich subregions in the promoter of the Septin9 gene and an internal control in a single reaction. ColonUSK proved increased sensitivity, with a detection limit as low as 12pg of the positive DNA compared with the Septin9 assay targeting one CpG-rich subregion. 1366 subjects were prospectively recruited from four comprehensive hospitals in China in an opportunistic screening study for assessing its value in CRC detection. Blind testing was developed to evaluate ColonUSK in comparison with clinical examination using clinical gold standard such as colonoscopy. RESULTS: The assay demonstrates clinical sensitivity for diagnosing colorectal cancer (CRC) and advanced adenoma at rates of 77.34% and 25.26%, respectively. Furthermore, ColonUSK exhibits a high degree of specificity for non-CRC cases (95.95%) clinically. Significantly, the detection rate of cases in high-grade intraepithelial neoplasia increased to 54.29%. The value for the assay in the Kappa test was 0.76, showing a high degree of consistency between ColonUSK and clinical gold standard. CONCLUSIONS: ColonUSK indicated moderate diagnostic value and could become a non-invasive detection way for CRC. The implementation of the ColonUSK assay has the capacity to markedly enhance CRC screening practices.

SIRT6 Inhibits Anoikis of Colorectal Cancer Cells by Down-Regulating NDRG1.

Anoikis, a form of apoptosis resulting from the loss of cell-extracellular matrix interaction, is a significant barrier to cancer cell metastasis. However, the epigenetic regulation of this process remains to be explored. Here, we demonstrate that the histone deacetylase sirtuin 6 (SIRT6) plays a pivotal role in conferring anoikis resistance to colorectal cancer (CRC) cells. The protein level of SIRT6 is negatively correlated with anoikis in CRC cells. The overexpression of SIRT6 decreases while the knockdown of SIRT6 increases detachment-induced anoikis. Mechanistically, SIRT6 inhibits the transcription of N-myc downstream-regulated gene 1 (NDRG1), a negative regulator of the AKT signaling pathway. We observed the up-regulation of SIRT6 in advanced-stage CRC samples. Together, our findings unveil a novel epigenetic program regulating the anoikis of CRC cells.

In situ fabrication of Fe3C nanoparticles and porous-carbon composites as high-performance electromagnetic wave absorber.

This study successfully utilized a straightforward approach, choosing liquid-liquid phase separation to build a porous structure and synthesize composite absorbers based on polyimide-based porous carbon/Fe3C (PIC/Fe3C-1, PIC/Fe3C-2) nanoparticles and porous carbon/FeCo alloy nanoparticles (PIC/FeCo). The specially designed network structure pore structures contributed multiple reflection, conduction loss and strong interfacial polarization. After characterization, PIC/Fe3C-2 obtained minimum RL of -35.37 dB at 17.04 GHz with 1.55 mm thickness and effective absorption bandwidth of 4.95 GHz with 1.66 mm thickness. Furthermore, PIC/FeCo, with a thickness of 1.63 mm, exhibits the most robust electromagnetic wave loss ability at 15.6 GHz, with a minimum RL of -56.32 dB and an effective absorption bandwidth of 4.88 GHz. Thus, the design strategy presented in this study could serve as a model for synthesizing other high-performance absorbers, effectively mitigating electromagnetic wave-induced pollution.

Developing Salt-Rejecting Evaporators for Solar Desalination: A Critical Review.

Solar desalination, a green, low-cost, and sustainable technology, offers a promising way to get clean water from seawater without relying on electricity and complex infrastructures. However, the main challenge faced in solar desalination is salt accumulation, either on the surface of or inside the solar evaporator, which can impair solar-to-vapor efficiency and even lead to the failure of the evaporator itself. While many ideas have been tried to address this ″salt accumulation″, scientists have not had a clear system for understanding what works best for the enhancement of salt-rejecting ability. Therein, for the first time, we classified the state-of-the-art salt-rejecting designs into isolation strategy (isolating the solar evaporator from brine), dilution strategy (diluting the concentrated brine), and crystallization strategy (regulating the crystallization site into a tiny area). Through the specific equations presented, we have identified key parameters for each strategy and highlighted the corresponding improvements in the solar desalination performance. This Review provides a semiquantitative perspective on salt-rejecting designs and critical parameters for enhancing the salt-rejecting ability of dilution-based, isolation-based, and crystallization-based solar evaporators. Ultimately, this knowledge can help us create reliable solar desalination solutions to provide clean water from even the saltiest sources.

Impact of thermal ultrasound on enzyme inactivation and flavor improvement of sea cucumber hydrolysates.

In this study, the effects of the thermal ultrasonic enzyme inactivation process on flavor enhancement in sea cucumber hydrolysates (SCHs) and its impact on the inactivation of neutral proteases (NPs) were investigated. The body wall of the sea cucumber was enzymatically hydrolyzed with NPs. On the one hand, the structure of NPs subjected to different enzyme inactivation methods was analyzed using ζ-potential, particle size, and Fourier transform infrared (FT-IR) spectroscopy. On the other hand, the microstructure and flavor changes of SCHs were examined through scanning electron microscopy, E-nose, and gas chromatography-ion mobility spectrometry (GC-IMS). The results indicated that thermal ultrasound treatment at 60 °C could greatly affect the structure of NPs, thereby achieving enzyme inactivation. Furthermore, this treatment generated more pleasant flavor compounds, such as pentanal and (E)-2-nonenal. Hence, thermal ultrasound treatment could serve as an alternative process to traditional heat inactivation of enzymes for improving the flavor of SCHs.

Theoretical study on the effect of shear deformation on MoTe2 as cathode material for calcium ion batteries.

CONTEXT: In this study, the electronic structure and diffusion barrier of Ca adsorbed MoTe2 system under different degrees of shear deformation were calculated based on the first-principles method. The results show that both the pure MoTe2 system and Ca-adsorbed MoTe2 system are affected by shear deformation. The pure MoTe2 undergoes a transition from direct to indirect band gap under shear deformation. The adsorption of Ca makes MoTe2 changes from semiconductor to quasi-metal. The results of the density of states show that Ca insertion makes the conduction band part of the adsorption system significantly enhanced. The diffusion barrier of Ca through MoTe2 indicates that the shear deformation promotes the diffusion of Ca on the surface of MoTe2. Shear deformation can effectively modulate the electronic properties of the MoTe2 system, which provides a theoretical basis for the application of MoTe2 materials in the field of ion batteries. METHODS: In this study, Materials Studio 8.0 software was used to construct the MoTe2 model and Ca adsorbed MoTe2 model, and the CASTEP module was used for first-principles calculation.

Polyimide-based porous carbon and cobalt nanoparticle composites as high-performance electromagnetic wave absorbers.

This study successfully utilized a straightforward approach, choosing liquid-liquid phase separation to build a porous structure and synthesize composite absorbers based on polyimide-based porous carbon and cobalt nanoparticles (designated as PPC/Co-700 and PPC/Co-800). A fine porous structure was achieved as a result of the excellent heat resistance of polyimide resulting in an excellent electromagnetic wave absorption ability of PPC/Co composites. The results obtained clearly indicated that PPC/Co-700 and PPC/Co-800 exhibit a porous structure with coral-like pores, enhancing both impedance matching properties and microwave attenuation abilities. This improvement in impedance matching conditions and dissipation capability is attributed to the synergistic effect of dielectric loss induced by carbon and magnetic loss induced by Co nanoparticles. PPC/Co-700 showed the strongest absorption performance with a minimum reflection loss of -59.85 dB (30 wt% loading, thickness of 3.42 mm) and an effective absorption bandwidth (EABW, RL ≤ -10 dB) of 6.24 GHz (30 wt% loading, thickness of 2.78 mm). Therefore, this work provides a facile strategy for the development of a promising absorbing material with outstanding electromagnetic wave absorption performance.

Improving Wear Resistance and Corrosive Resistance of Cemented Carbide for Mud Pulser Rotor by Deep Cryogenic Treatment.

Cemented carbide used in the rotor of a mud pulser is subjected to the scouring action of solid particles and corrosive mud media for a long time, which causes abrasive wear and electrochemical corrosion. To improve the wear and corrosive resistance of cemented carbide, samples with different cobalt content (WC-5Co, WC-8Co, and WC-10Co) receive deep cryogenic treatment (DCT) at -196 °C for 2.5 h. An optical metalloscope (OM) and X-ray diffractometer (XRD) are used to observe the phase changes of cemented carbides, and the XRD is also used to observe the change in residual stress on the cemented carbide's surface. A scanning electron microscope (SEM) is used to characterize the wear and electrochemical corrosion surface microstructure of cemented carbides (untreated and DCT). The results show that the DCT promotes the precipitation of the η phase, and the diffraction peak of ε-Co tends to intensify. Compared with the untreated, the wear rates of WC-5Co, WC-8Co, and WC-10Co can be reduced by 14.71%, 37.25%, and 41.01% by DCT, respectively. The wear form of the cemented carbides is mainly the extrusion deformation of Co and WC shedding. The precipitation of the η phase and the increase in WC residual compressive stress by DCT are the main reasons for the improvement of wear resistance. The electrochemical corrosion characteristic is the dissolution of the Co phase. DCT causes the corrosion potential of cemented carbide to shift forward and the corrosion current density to decrease. The enhancement of the corrosion resistance of cemented carbide caused by DCT is due to the Co phase transition, η phase precipitation, and the increase in the compressive stress of cemented carbide.

Comparison and discussion of behavior and pathology of four kinds of cerebral palsy disease models.

Explore the differences in behavioral and pathological manifestations of rat models of cerebral palsy made by different methods and discuss what types of studies these models are suitable for. Behavioral evaluation and pathological section observation were used to observe and evaluate the model. Conclusion: except for the absence of data of bilateral common carotid artery ligation rats, the other three methods could all achieve a successful cerebral palsy disease model for both behavioral and pathological. For researchers, the selection of intraperitoneal infection model in pregnant rats or unilateral ischemia and hypoxia model in infant rats is sufficient to meet the experimental needs, whereas the selection of the combined method for modeling does not show enough advantages, which not only causes the waste of financial and human resources but also increases the possibility of experimental error made by intervention factors.

lncRNA-MIAT rs9625066 polymorphism could be a potential biomarker for ischemic stroke.

BACKGROUND: Ischemic stroke (IS) is a common and serious neurological condition that is highly fatal but so far no early diagnostic markers are available. Myocardial infarction-associated transcript (MIAT) is a long non-coding RNA (lncRNA) that could lead to IS by inducing autophagy and apoptosis in neuronal cells. However, there has been no report on the link between susceptibility to IS and the single-nucleotide polymorphisms (SNPs) of MIAT. This study aimed to investigate the association between MIAT gene polymorphisms and IS risk. METHODS: A total of 320 IS patients and 310 age-, sex- and race-matched controls were included in this study. Four polymorphisms (rs2157598, rs5761664, rs1894720, and rs9625066) were genotyped by using SNPscan technique. RESULTS: Among the 4 polymorphisms of MIAT, only rs9625066 was associated with IS risk (CA vs. CC: adjusted OR = 0.55, 95% CI, 0.37-0.85, P = 0.006; AA vs. CC: adjusted OR = 0.39, 95% CI, 0.16-0.94, P = 0.036; (AA + CA vs. CC: adjusted OR = 0.53, 95% CI, 0.35-0.80, P = 0.002; A vs. C adjusted OR = 0.59, 95% CI, 0.42-0.82, P = 0.002). Haplotype analysis showed a 1.32-fold increase (95% CI, 1.05-1.67, P = 0.017) in IS risk for rs2157598-rs5761664-rs1894720-rs9625066 (A-C-G-C). Logistic regression analysis identified some independent impact factors for IS including rs9625066 AA/AC, TC, TG, HDL-C (P < 0.05). CONCLUSION: The rs9625066 polymorphism of MIAT might be associated with IS susceptibility in Chinese population, in which AA/CA plays a protective role in IS, whereas the CC genotype increases the risk of developing IS, suggesting it might be a marker predictive of IS risk.

Revision of residual deformities after primary surgery for Wassel-Flatt IV-D thumb duplication using a microsurgical free lateral great toe flap.

We report the application and results of skin defect coverage using the free lateral great toe flap in revision surgery for residual postoperative deformities in Wassel-Flatt type IV-D thumb duplications. This retrospective study included five patients treated between June 2020 and September 2021 to correct angular deformity and repair the secondary skin defect. All the flaps survived. The patients were followed up for 8-12 months and all the reconstructed thumbs had a satisfactory appearance. The results of the Japanese Society for Surgery of the Hand scoring system were excellent in one patient, good in three patients and fair in one patient. The results of the Alignment, Ulnar and Radial stability, Range of motion and Aesthetical aspects (ALURRA) scoring system were good in four patients and moderate in one patient.Level of evidence: IV.

Design of Thick Electrodes with Vertical Channels for Aqueous Batteries: Experimental and Numerical Analysis.

Developing thick electrodes with high-area loadings is a direct method for boosting the energy density. However, this approach also leads to a proportional increase in the resistance to charge transport. Optimizing the microstructure of the electrode can effectively enhance the charge transport kinetics in thick electrodes. Herein, a low-tortuosity nickel electrode with vertical channels (VC-Ni) is fabricated using a phase inversion method. A high-loading VC-Ni electrode (26.7 mg cm-2) delivers a superior specific capacity of 134.0 mAh g-1 at a 5 C rate, significantly outperforming the conventional nickel electrode (Con-Ni). Numerical simulations reveal the fast transport kinetics within the vertical channel electrodes. For the thick electrode, the VC-Ni electrode shows a substantially lower concentration gradient of OH- and H+ compared to the Con-Ni electrode. Notably, beyond a critical loading of 26.5 mg cm-2, the specific capacity initially increases with volume fraction, peaking at 50%, and then diminishes. The specific capacity increases as the channel size decreases, but the tendency to increase gradually decreases. The highest specific capacity is achieved with an inverted trapezoidal channel shape, characterized by larger pores near the separator and smaller pores near the current collector. This work is of guidance for the design of thick electrodes for high-performance aqueous batteries.

Dearomatization of Pyridines: Stereoselective Synthesis of Functionalized [1,2,4]Triazolo[4,3-a]pyridines.

The stereoselective preparation of functionalized [1,2,4]triazolo[4,3-a]pyridines from N-tosylhydrazones and pyridines was developed through the dearomatization of pyridines. The current transformation features good step- and atom-economy, high diastereoselectivity, and the efficient formation of four new carbon-heteroatom bonds in the corresponding product tetrahydro pyridines.

The use of the ratio of C-reactive protein to albumin for the diagnosis of pediatric septic arthritis.

Purpose: This study aimed to investigate the relationship between the ratio of c-reactive protein to albumin (CAR) and pediatric septic arthritis (PSA). Methods: Clinical and laboratory data were collected. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive ability of CAR in identifying PSA. Multivariable logistic regression analyses was performed to calculate adjusted odds ratio (OR) with 95% confidence interval (CI). Results: We included 305 patients with PSA (CAR ≤ 0.447, 182 patients; CAR > 0.447, 123 patients) between September 2013 and November 2022. ROC analysis showed that CAR performed best in diagnosing PSA, with an area under curve (AUC) value of 0.828. After adjusted for potential confounders, we found that high CAR was associated with PSA (OR = 6.85, 95% CI: 2.30-20.40, p = 0.001). In sensitivity analyses, subgroups analyses, and propensity score matching, the results remain stable. Conclusions: The CAR (>0.447) at admission was an independent risk factor for PSA. It is worthy to further investigate this association.