Decreasing of serine/threonine kinase 39 has tumour inhibiting effects on acute myeloid leukaemia by impacting the PI3K/AKT and Wnt/ß-catenin signalling cascades.

Serine/threonine kinase 39 (STK39) has been identified as a key regulator of tumour progression. However, whether STK39 plays a role in acute myeloid leukaemia (AML) remains undetermined. This work explored the expression and functions of STK39 in AML. STK39 was found to be overexpressed in AML and was negatively correlated with overall survival. Functionally, silencing STK39 inhibited cell proliferation, promoted cell differentiation and induced cell cycle arrest and apoptosis. The tumour inhibiting effects of STK39 downregulation were also verified by an in vivo xenograft tumour assay. Mechanistically, STK39 was closely related to the PI3K/AKT and Wnt/ß-catenin signalling cascades in AML. Silencing of STK39 had suppressive effects on the PI3K/AKT and Wnt/ß-catenin signalling cascades. The suppressive effect of STK39 silencing on the Wnt/ß-catenin signalling cascade was significantly reversed when PI3K/AKT was reactivated. When ß-catenin was re-expressed, the tumour-inhibiting effects caused by STK39 silencing were significantly eliminated. Therefore, STK39 plays a crucial role in AML and could be targeted for potential therapeutic purposes in treating AML.

Pickering Emulsion Templated 3D Cylindrical Open Porous Aerogel for Highly Efficient Solar Steam Generation.

Porous-structured evaporators have been fabricated for achieving a high clean water throughput due to their maximized surface area. However, most of the evaporation surfaces in the porous structure are not active because of the trapped vapor in pores. Herein, a three-dimensional (3D) cylindrical aerogel-based photothermal evaporator with a disordered interconnected hierarchical porous structure is developed via a Pickering emulsion-involved polymerization method. The obtained cotton cellulose/aramid nanofibers/polypyrrole (CAP) aerogel-based evaporator achieved all-cold evaporation under 1.0 sun irradiation, which not only completely eliminated energy loss via radiation, convection, and conduction, but also harvested massive extra energy from the surrounding environment and bulk water, thus significantly increasing the total energy input for vapor generation to deliver an extremely high evaporation rate of 5.368 kg m-2 h-1 . In addition, with the external convective flow, solar steam generation over the evaporator can be dramatically enhanced due to fast vapor diffusion out of its unique opened porous structure, realizing an ultrahigh evaporation rate of 18.539 kg m-2 h-1 under 1.0 sun and 4.0 m s-1 . Moreover, this evaporator can continuously operate with concentrated salt solution (20 wt.% NaCl). This work advances rational design and construction of solar evaporator to promote the application of solar evaporation technology in freshwater production.

CaMKK2 alleviates myocardial ischemia/reperfusion injury by inhibiting oxidative stress and inflammation via the action on the AMPK-AKT-GSK-3ß/Nrf2 signaling cascade.

OBJECTIVE: Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) can regulate numerous biological processes and is implicated in diverse pathological processes. Yet its role in myocardial ischemia/reperfusion (MI/R) injury remains unknown. This project explored the possible functions and mechanisms of CaMKK2 in MI/R injury. METHODS: A rat model of MI/R in vivo was established using the left anterior descending coronary artery ligation method. Rat cardiomyocytes were exposed to hypoxia/reoxygenation (H/R) in vitro to establish a cell model. Overexpression of CaMKK2 was achieved by infecting recombinant adeno-associated virus or adenovirus expressing CaMKK2. Real-time quantitative PCR, immunoblotting, TTC staining, TUNEL assay, ELISA, oxidative stress detection assays, flow cytometry, and CCK-8 assay were carried out. RESULTS: A decline in CaMKK2 levels was induced by MI/R in vivo or H/R in vitro. Up-modulation of CaMKK2 in rats ameliorated the cardiac injury evoked by MI/R injury accompanied by suppression of cardiac apoptosis, oxidative stress, and proinflammatory response. Rat cardiomyocytes with CaMKK2 overexpression were also protected from H/R damage by inhibiting apoptosis, oxidative stress, and proinflammatory response. CaMKK2 overexpression led to increased phosphorylation of AMPK, AKT, and GSK-3ß, and enhanced activation of Nrf2 under MI/R or H/R conditions. Inhibition of AMPK abolished CaMKK2-mediated Nrf2 activation and relevant cardioprotective effect. Restraint of Nrf2 also diminished CaMKK2-mediated relevant cardioprotective effect. CONCLUSIONS: Up-regulation of CaMKK2 provides a therapeutic benefit in the rat model of MI/R injury by boosting the Nrf2 pathway through regulation of AMPK/AKT/GSK-3ß, which suggests CaMKK2 as a new molecular target for the treatment of MI/R injury.

Platycodon grandifloras polysaccharides inhibit mitophagy injury induced by Cr (VI) in DF-1 cells.

This study aimed to investigate the role of Platycodon grandiflorus polysaccharide (PGPS) in chromium (VI)-induced autophagy in a chicken embryo fibroblast cell lines (DF-1 cells). DF-1 cells were exposed to Cr (VI), PGPSt, and Cr (VI) + PGPSt, and their effects on cell viability, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and autophagy-related proteins were examined. The results showed that the cell viability was reduced after Cr (VI) treatment, and 3-MA, CsA or PGPSt suppressed this decrease. Cr (VI) treatment increased the ROS levels and decreased the MMP, thereby enhancing the expression of mitochondrial autophagy marker proteins (PINK1, Parkin, and LC3-II), inhibiting mitophagy autophagy protein TOMM20 expression, and promoting the degradation of autophagy-related marker p62. These changes led to exceeding mitochondrial autophagy and cell trauma and could be mitigated by PGPSt. Overall, our research showed that Cr (VI) can induce exceeding mitochondrial autophagy in DF-1 cells, whereas PGPSt can improve Cr (VI)-induced mitochondrial autophagy by inhibiting ROS and restoring MMP.

Health Monitoring of Bolted Spherical Joint Connection Based on Active Sensing Technique Using Piezoceramic Transducers.

Bolted spherical joints are widely used to form space steel structures. The stiffness and load capacity of the structures are affected by the looseness of bolted spherical joint connections in the structures. The looseness of the connections, which can be caused by fabrication error, low modeling accuracy, and "false twist" in the installation process, may negatively impact the load capacity of the structure and even lead to severe accidents. Furthermore, it is difficult to detect bolted spherical joint connection looseness from the outside since the bolts connect spheres with rods together from the inside. Active sensing methods are proposed in this paper to monitor the tightness status of the bolted spherical connection using piezoceramic transducers. A triangle-on-triangle offset grid composed of bolted spherical joints and steel tube bars was fabricated as the specimen and was used to validate the active sensing methods. Lead Zirconate Titanate (PZT) patches were used as sensors and actuators to monitor the bolted spherical joint tightness status. One PZT patch mounted on the central bolted sphere at the upper chord was used as an actuator to generate a stress wave. Another PZT patch mounted on the bar was used as a sensor to detect the propagated waves through the bolted spherical connection. The looseness of the connection can impact the energy of the stress wave propagated through the connection. The wavelet packet analysis and time reversal (TR) method were used to quantify the energy of the transmitted signal between the PZT patches by which the tightness status of the connection can be detected. In order to verify the effectiveness, repeatability, and consistency of the proposed methods, the experiments were repeated six times in different bolted spherical connection positions. The experimental results showed that the wavelet packet analysis and TR method are effective in detecting the tightness status of the connections. The proposed active monitoring method using PZT transducers can monitor the tightness levels of bolted spherical joint connections efficiently and shows its potential to guarantee the safety of space steel structures in construction and service.

Drug-associated congenital anomalies of the external ear identified in the United States food and drug administration adverse event reporting system database.

Congenital anomalies of the external ear can have a significant impact on a child's development and quality of life. While genetic factors play a crucial role in the etiology of these anomalies, environmental factors such as drug exposure during pregnancy may also contribute to their occurrence. This study aims to investigate the association between drug exposure and congenital anomalies of the external ear using data from an adverse drug reaction report database. Using OpenVigil 2.1, we queried the FAERS database to retrieve adverse event reports from the first quarter of 2004 to the first quarter of 2024. To identify relevant cases, we used Medical Dictionary for Regulatory Activities terms focusing on congenital anomalies of the external ear. Drug generic names were sourced from the DrugBank database. To assess safety signals and rank drugs by their signal strength, we conducted a disproportionality analysis, generating reporting odds ratios (ROR) and proportional reporting ratios (PRR). A total of 20,754,281 AE reports were identified in the FAERS database from Q1 2004 to Q1 2024, of which 1763 were related to congenital anomalies of the external ear. Valproic acid (122 cases) was associated with the most cases, followed by mycophenolate mofetil (105 cases) and lamotrigine (65 cases). According to the disproportionality analysis, the top five drugs with the highest ROR and PRR were primidone (ROR: 397.05, 95% CI 147.21, 1070.9; PRR: 388.71, 95% CI 145.89, 1035.7), valproic acid (ROR: 239.46, 95% CI 123.75, 463.37; PRR: 236.42, 95% CI 123.82, 451.43), tapazole (ROR: 198.35, 95% CI 63.49, 619.67; PRR: 196.25, 95% CI 62.97, 611.67), nevirapine (ROR: 138.24, 95% CI 82.9, 230.51; PRR: 137.23, 95% CI 82.44, 228.44), and sebivo (ROR: 117.1, 95% CI 48.51, 282.67; PRR: 116.37, 95% CI 48.17, 281.12). This study identified several drugs significantly associated with congenital anomalies of the external ear in the FAERS database using disproportionality analysis. The findings can help healthcare professionals better recognize and manage drug-induced congenital anomalies of the external ear, particularly when prescribing high-risk medications. Further research is needed to elucidate the mechanisms underlying these associations and develop strategies for preventing and mitigating drug-induced congenital anomalies of the external ear.

Enhanced non-radical activation of persulfate with pompon-like NiO microspheres for removing sulfamethoxazole in water.

The development of efficient heterogeneous catalyst for non-radical activation of persulfate (PS) is highly desired for removing organic pollutants in water. Herein, four NiO samples were prepared by different methods, and their performance for PS activation was investigated using sulfamethoxazole (SMX) as the target pollutant. The structure, surface chemical state, and redox ability of these samples were measured by various characterization techniques, and the key property affecting PS activation efficiency was explored. The results showed that the degradation of SMX by these samples all followed the non-radical mechanism, and the activated PS was the dominant active species. Among them, pompon-like NiO microspheres exhibited the highest activity due to its large surface area and especially high oxidation ability. Catalyst with high oxidation ability or reducing ability should facilitate the non-radical or radical activation of PS, respectively. SMX was completely removed by pompon-like NiO microspheres within 10 min, and the reaction rate constant was calculated to be 0.4199 min-1. An adsorption-degradation experiment was designed to verify the high stability and oxidation potential of the adsorbed PS on NiO surface. Pompon-like NiO microspheres exhibited good reusability, and its performance was barely affected by water quality, demonstrating its potential application in water treatment.

Tough Adhesive, Antifreezing, and Antidrying Natural Globulin-Based Organohydrogels for Strain Sensors.

Hydrogels are often used to fabricate strain sensors; however, they also suffer from freezing at low temperatures and become dry during long-time storage. Encapsulation of hydrogels with elastomers is one of the methods to solve these problems although the adhesion between hydrogels and elastomers is usually low. In this work, using bovine serum protein (BSA) as the natural globulin model and glycerol/H2O as the mixture solvent, BSA/polyacrylamide organohydrogels (BSA/PAAm OHGs) were prepared by a facile photopolymerization approach. At the optimal condition, BSA/PAAm OHG demonstrated not only high toughness but also tough adhesion properties, which could strongly adhere to various substrates, such as glass, metals, rigid polymeric materials (even poly(tetrafluoroethylene), i.e., PTFE), and soft elastomers. Moreover, BSA/PAAm OHG was flexible and showed tough adhesion at -20 °C. The toughening mechanism and the adhesive mechanism were proposed. On being encapsulated by poly(dimethylsiloxane) (PDMS), it illustrated good antidrying performance. After introducing a conductive filler, the encapsulated BSA/PAAm OHG could be used as a strain sensor to detect human motions. This work provides a better understanding of the adhesive mechanism of natural protein-based organohydrogels.

Using a mixed method to identify communication skills training priorities for Chinese general practitioners in diabetes care.

BACKGROUND: In China diabetes care is gradually shifting from secondary to primary care with great infrastructure investment and GP training. However, most GPs in China lack communication skills training, which is a huge obstacle in communication with their patients in primary care. In this study we seek to identify training priorities that is evidence-based, appropriate for the context of primary care in China, and that meet the real needs of both GPs and people with diabetes. METHODS: A mixed method approach was used. A conceptual framework was designed based on the MRC framework, action research and adult learning theories. Through a systematic review of the literature and qualitative research with GPs and patients with diabetes, a list of communication skills training components was developed by the research team. A modified nominal group technique (NGT) with GPs was used to evaluate these contents. Purposive sampling was used to recruit a variation of participants (age, work area, practice years and education background) from general practices in Guangzhou city, China. Eight structured nominal groups were facilitated to elicit the views of group members, and participants rated the 9-point Likert scale of importance and feasibility of the training items independently, before and after focus groups. The ranking of each item was calculated, based on the mean Likert score ratings from all participants. Video recordings of four NGT group discussions were thematically analysed using the Framework Method to explore reasons for any differences in rating items. RESULTS: 29 males and 29 female GPs from 28 general practices participated in NGT group discussions, with a mean age of 38.5 years and mean 12.3 years of practice experience. Based on the mean scores of importance and feasibility rating scores, the top 3 ranked priorities for communication training were 'health education' (importance 8.39, feasibility 7.67), 'discussing and explaining blood glucose monitoring' (8.31, 7.46), and 'diabetes complications and cardiovascular disease risk communication' (8.36, 7.12). Five main themes were identified from focus group discussions through qualitative analysis: 'impact on diabetes patients', 'GP attitudes towards communication skills', 'patient-related factors influencing the application of communication skills by GPs, 'local contextual factors', and 'training implementation'. CONCLUSIONS: Priorities for communication skills training for Chinese GPs in diabetes care were identified. These are set in the context of GPs' current experience of communication with patients in China who have diabetes, which is often unsatisfactory. This study describes the baseline from which better primary care for diabetes in China needs to be developed. Based on suggestions from GPs themselves, it identifies an agenda for improvement in communication as a key component of diabetes care in China.

Pharmacokinetic study of lappaconitine hydrobromide in mice by LC-MS.

A high sensitive and rapid method was developed for the analysis of lappaconitine in mouse plasma using liquid chromatography coupled to mass spectrometry (LC-MS). Detection was performed by positive ion electrospray ionization (ESI) in multiple reaction monitoring (MRM) mode, monitoring the transitions m/z 585 --> m/z 535 and m/z 356 --> m/z 192, for the quantification of lappaconitine and tetrahydropalmatine (internal standard, IS), respectively. The method was linear over the concentration range of 3.0-2000.0 ng x mL(-1). The lower limit of quantification was 3.0 ng x mL(-1). Intra- and inter-run precisions (RSD) were both less than 9.9% and accuracy (RE) within +/- 4.8%. After single intravenous injections of lappaconitine hydrobromide at 1.0, 2.0 and 4.0 mg x kg(-1), the elimination half-lives (t(1/2)) were 0.47, 0.48 and 0.49 h, and the areas under the curve (AUC(0-t)) were 55.5, 110.5 and 402.9 ng x h x mL(-1), separately. The pharmacokinetic profile of lappaconitine was linear at relatively lower dose levels (1.0-2.0 mg x kg(-1)). When the dose increased farther to 4.0 mg x kg(-1), the Vz and CL decreased, and the increase fold of the AUC was much larger than that of the dose.

[Monitoring "green tide" in the Yellow Sea and the East China Sea using multi-temporal and multi-source remote sensing images].

Landsat-TM (Theme Mapper) and EOS (Earth Observing System)-MODIS (MODerate resolution Imaging Spectrora-diometer) Terra/Aqua images were used to monitor the macro-algae (Ulva prolifera) bloom since 2007 at the Yellow Sea and the East China Sea. At the turbid waters of Northern Jiangsu Shoal, there is strong spectral mixing behavior, and satellite images with finer spatical resolution are more effective in detection of macro-algae patches. Macro-algae patches were detected by the Landsat images for the first time at the Sheyang estuary where is dominated by very turbid waters. The MODIS images showed that the macro-algae from the turbid waters near the Northern Jiangsu Shoal drifted southwardly in the early of May and affected the East China Sea waters; with the strengthening east-asian Summer Monsoon, macro-algae patches mainly drifted in a northward path which was mostly observed at the Yellow Sea. Macro-algae patches were also found to drift eastwardly towards the Korea Peninsular, which are supposed to be driven by the sea surface wind.

A series of molecular modeling techniques to reveal selective mechanisms of inhibitors to ß-Site amyloid precursor protein cleaving enzyme 1 (BACE1) and ß-site amyloid precursor protein cleaving enzyme 2 (BACE2).

Inhibition of ß-Site amyloid precursor protein cleaving enzyme 1 (BACE1) has been shown to be an effective treatment for Alzheimer's disease. A wealth of research has focused on finding highly selective small-molecule inhibitors targeting the BACE1 over its close homologue BACE2 to avoid potential side effects. However, given the highly structural similarities of BACE1 and BACE2, designing highly selective BACE1 inhibitors remains a huge challenge. Recently, it has been reported that a potential BACE1 inhibitor named C28 (∼52-fold selectivity) exhibited greater selectivity to BACE1 over BACE2 than the previously reported inhibitors AZD3293 and AZD3839 (∼1.5-fold and 14-fold selectivity). However, few computational studies have been performed to reveal its underlying mechanisms. In this study, a series of molecular modeling techniques were performed to reveal the selective mechanisms. Classical molecular dynamics (cMD) simulations indicated that the major variations appeared to be controlled by overall protein dynamics. Free energy calculations further suggested that the binding affinities of AZD3293 to BACE1 and BACE2 are similar, but the binding affinity of AZD3839 and C28 to BACE1 is much higher than to BACE2, and that the major variations are electrostatic interactions. The protein dynamics and energy differences were further observed in accelerated molecular dynamics (aMD) simulations. In addition, the umbrella sampling simulations revealed the inhibitors' different patterns of dissociation from the binding pockets of BACE1 and BACE2, and that different energy barriers were responsible for the selectivity. The physical principles revealed by this study may facilitate the rational design of more potent BACE1 selective inhibitors. Communicated by Ramaswamy H. Sarma.

The role of ATF6 in Cr(VI)-induced apoptosis in DF-1 cells.

Hexavalent chromium (Cr(VI)) is a common heavy metal pollutant in environment and has been proved possessing the cytotoxicity. In this study, we aimed to investigate the role of activating transcription factor 6 (ATF-6) in apoptosis of chicken embryo fibroblasts cell line (DF-1) induced by Cr(VI). Firstly, DF-1 cells were exposed to Cr(VI) to establish the cytotoxicity model, then the cell apoptosis and ATF-6 protein level were analyzed. By silencing ATF-6 gene, changes of the apoptosis rate and apoptotic proteins were examined. To further explore the regulatory mechanism of ATF-6, endoplasmic reticulum (ER) stress, mitochondrial function, reactive oxygen species (ROS) level, as well as the related pathway were evaluated. Results showed that Cr(VI) can result in DF-1 cell apoptosis, along with mitochondrial membrane potential (MMP) reducing and ER stress. Meanwhile, ATF-6 silencing lowered the apoptosis rate and ER stress level, showing with the decrease of XBP-1, PERK, GRP78, Caspase-12, Cleaved Caspase-3 and the increase of Bcl-2. Further analysis found that ATF-6 silencing down-regulated ROS and caused MMP loss, suggesting that ATF-6 silencing inhibited Cr(VI)-induced mitochondrial damage. In conclusion, this study indicate that ATF-6 plays an important regulatory role in Cr(VI)-induced DF-1 cell apoptosis through the ER stress and mitochondrial pathway.

Inflammatory injury and mitophagy induced by Cr(VI) in chicken liver.

Cr(VI) is a widely used chemical. Excessive Cr(VI) exposure not only causes inflammatory damage but also induces mitophagy. This study aimed to demonstrate the effect of Cr(VI) on inflammatory injury and mitophagy in chicken liver. A total of 120 Hyland Brown cockerels (1 day old) were randomly divided into four groups and orally treated with different Cr(VI) doses (10% median lethal dose, 6% median lethal dose, 2% median lethal dose, and 0% median lethal dose) daily for 45 days to explore the underlying mechanism. Results showed that excessive Cr(VI) increased tumor necrosis factor-α, interleukin-6, and heat shock protein but decreased interferon-γ expression and adenosine triphosphate content in chicken liver. Cr(VI) significantly increased reactive oxygen species production, induced mitochondrial membrane potential collapse, and promoted autophagosome formation. Cr(VI) treatment also caused an increase in LC3-II, stimulated Parkin translocation, and inhibited the expression of p62/SQSTM1 and translocase of outer mitochondrial membrane 20. Therefore, excessive Cr(VI) caused inflammatory damage and mitophagy in chicken liver.

Effects of Cr(VI) exposure on electrocardiogram, myocardial enzyme parameters, inflammatory factors, oxidative kinase, and ATPase of the heart in Chinese rural dogs.

Heavily chromium-polluted areas, where people are prohibited from entering, are paradises for stray dogs. In this study, stray dogs were used to study the effects of chromium exposure on the heart of dogs in severely Cr(VI)-contaminated rural areas of China. The dogs were given water (control), low dose (L, 0.92 mg/kg), medium dose (M, 1.15 mg/kg), and high dose (H, 1.38 mg/kg) of Cr(VI). The changes of electrocardiogram (ECG), myocardial enzyme parameters, inflammatory factors, oxidative kinase, and ATPase were measured to determine the toxicity of chromium on the heart of dogs. Results showed that the ST segment of ECG increased significantly, and the amplitude of T wave increased in the experimental group. The myocardial enzyme (CK-MB, AST, CK, and LDH) content in groups M and H increased significantly over time. The values of CAT, T-SOD, IL-10, and ATPase (K+-Na+-ATPase and Ca2+-Mg2+-ATPase) decreased with the increase of Cr(VI) dose, and the content of MDA, IL-1ß, IL-8, and TNF-α increased with the increase of Cr(VI) dose. Our study suggested that the heart of Chinese rural dog was damaged by Cr(VI), and Cr(VI) could cause oxidative damage and alteration of ATPase content in dogs.

A facile and green approach to prepare carbon dots with pH-dependent fluorescence for patterning and bioimaging.

As the new representative in the carbonaceous family, carbon dots (CDs) have gained remarkable research interests over the past decade. Herein, we report the facile preparation and thorough performance comparison of three types of carbon dots with the adoption of ubiquitous natural fruit juice as precursors and demonstrate their application in pH sensing, patterning and bioimaging. All the yielded CDs show interesting optical properties including evident single- or two-photon absorption and excitation-dependent photoluminescence along with the high fluorescent yield. A detailed study on the physical properties by EPR and Stokes shift analysis and structural composition analysis by XPS and Raman spectroscopy suggest that the fluorescence of CDs originates from the electron-hole recombination via the defect state. In addition, through the regulation of non-radiative recombination rate of CDs, all the obtained CDs could be applied as fluorescent sensing platforms toward the sensitive detection of the solution pH changes by the indication of CDs' fluorescent yield and lifetime variation. Moreover, it was also proven that the resulting CDs could be employed as fluorescent inks for printing patterns in anti-counterfeit applications and as fluorescent probes for bioimaging of osteoblasts.

Effect and mechanism of penetration enhancement of organic base and alcohol on glycyrrhetinic acid in vitro.

The aim of the present study was to explore the effects of organic bases and alcohols on the percutaneous absorption of Glycyrrhetinic acid (GA). GA is a metabolite of Glycyrrhizic acid (GL), a major active ingredient of Glycyrrhizae (Gancao) Radices. Skin penetration parameters of GA were obtained via in vitro penetration experiments using intact and stripped mice back skin. Non-aqueous solvent comprising isopropyl myristate (IPM) and alcohols (ethanol, butanol, octanol and dodecanol) loaded with organic base (triethanolamine or triethylamine) were applied to improve the penetration of GA. In order to further confirm the mechanism by which the organic bases enhanced the penetration of GA, conductivity measurement, (1)H NMR spectroscopy and FT-IR analysis were used to observe the formation of ion pair between GA and organic base. The formation of ion pair increased the solubility of GA in the stratum corneum (SC) and its partition into the viable skin, and therefore enhanced the penetration of GA in skin.