Capturing RAS oligomerization on a membrane.

RAS GTPases associate with the biological membrane where they function as molecular switches to regulate cell growth. Recent studies indicate that RAS proteins oligomerize on membranes, and disrupting these assemblies represents an alternative therapeutic strategy. However, conflicting reports on RAS assemblies, ranging in size from dimers to nanoclusters, have brought to the fore key questions regarding the stoichiometry and parameters that influence oligomerization. Here, we probe three isoforms of RAS [Kirsten Rat Sarcoma viral oncogene (KRAS), Harvey Rat Sarcoma viral oncogene (HRAS), and Neuroblastoma oncogene (NRAS)] directly from membranes using mass spectrometry. We show that KRAS on membranes in the inactive state (GDP-bound) is monomeric but forms dimers in the active state (GTP-bound). We demonstrate that the small molecule BI2852 can induce dimerization of KRAS, whereas the binding of effector proteins disrupts dimerization. We also show that RAS dimerization is dependent on lipid composition and reveal that oligomerization of NRAS is regulated by palmitoylation. By monitoring the intrinsic GTPase activity of RAS, we capture the emergence of a dimer containing either mixed nucleotides or GDP on membranes. We find that the interaction of RAS with the catalytic domain of Son of Sevenless (SOScat) is influenced by membrane composition. We also capture the activation and monomer to dimer conversion of KRAS by SOScat. These results not only reveal the stoichiometry of RAS assemblies on membranes but also uncover the impact of critical factors on oligomerization, encompassing regulation by nucleotides, lipids, and palmitoylation.

SIRT1: An Intermediator of Key Pathways Regulating Pulmonary Diseases.

Silent information regulator type-1 (SIRT1), a nicotinamide adenine dinucleotide+-dependent deacetylase, is a member of the sirtuins family and has unique protein deacetylase activity. SIRT1 participates in physiological as well as pathophysiological processes by targeting a wide range of protein substrates and signalings. In this review, we described the latest progress of SIRT1 in pulmonary diseases. We have introduced the basic information and summarized the prominent role of SIRT1 in several lung diseases, such as acute lung injury, acute respiratory distress syndrome, chronic obstructive pulmonary disease, lung cancer, and aging-related diseases.

Rapid Sample Pretreatment Facilitating SERS Detection of Trace Weak Organic Acids/Bases in Complex Matrices.

Fast and efficient sample pretreatment is the prerequisite for realizing surface-enhanced Raman spectroscopy (SERS) detection of trace targets in complex matrices, which is still a big issue for the practical application of SERS. Recently, we have proposed a highly performed liquid-liquid extraction (LLE)-back extraction (BE) for weak acids/bases extraction in drinking water and beverage samples. However, the performance efficiency decreased drastically on facing matrices like food and biological blood. Based on the total interaction energies among target, interferent, and extractant molecules, solid-phase extraction (SPE) with a higher selectivity was introduced in advance of LLE-BE, which enabled the sensitive (µg L-1 level) and rapid (within 10 min) SERS detection of both koumine (a weak base) and celastrol (a weak acid) in different food and biological samples. Further, the high SERS sensitivity was determined unmanned by Vis-CAD (a machine learning algorithm), instead of the highly demanded expert recognition. The generality of SPE-LLE-BE for various weak acids/bases (2 < pKa < 12), accompanied by the high efficiency, easy operation, and low cost, offers SERS as a powerful on-site and efficient inspection tool in food safety and forensics.

Effective bandgap narrowing and enhanced optoelectronic performance of Cs2PtBr6 double perovskites by pressure engineering.

Tuning the structure-property relations of perovskites by pressure engineering holds great promise for discovering materials with favorable properties. The newly synthesized Cs2PtBr6 double perovskite exhibits excellent water resistance and chemical stability. Yet its photoelectric conversion efficiency is limited by its intrinsic wide-bandgap nature. In this work, based on density functional theory calculations, we demonstrate the bandgap narrowing of Cs2PtBr6 via pressure engineering and maintain its structural stability. Strikingly, upon applying pressure up to 12 GPa, the bandgap value decreases to 1.34 eV, which exactly reaches the optimal bandgap required by the Shockley-Queisser efficiency limit. Moreover, optical calculation analysis shows that the optical absorption of Cs2PtBr6 exhibits a significant improvement within the visible range. Therefore, the potential of Cs2PtBr6 as a photovoltaic material by pressure engineering is improved. This work is useful for designing and synthesizing new perovskite materials with enhanced performance.

Identification, molecular profiling and immune functions of cystatin M in silver pomfret (Pampus argenteus).

Cystatins play an important role in various physiological and pathological processes of organisms, including regulating protein metabolism, antigen processing, inflammatory response, nutritional disorders, and controlling enzyme activity. However, research on immunity functions of fish cystatin M is limited. In this study, Pampus argenteus cystatin M (Pacystatin M) was identified and analyzed. Its amino acid sequence was highly conserved in teleosts, and included the conserved cystatin cysteine protease inhibitor motifs. Pacystatin M was highly expressed in the gill, spleen, and intestine, whereas the expression levels of liver and kidney were lower. Furthermore, Nocardia seriolae infection up-regulated the expression of Pacystatin M in the kidney, spleen and liver, with particularly significant expression observed in the liver on day 15 post-infection. Functional analysis indicated that the recombinant Pacystatin M showed increasing inhibitory activity against papain within a certain concentration range, suggesting that the inhibition was likely competitive. Additionally, Pacystatin M demonstrated the ability to inhibit bacterial growth and high thermal stability. These results suggested that Pacystatin M might be involved in the immune response to microbial invasion and provided new reference addressing disease issues in the large-scale farming of silver pomfret.

Effects of vitamins and polyunsaturated fatty acids on cognitive function in older adults with mild cognitive impairment: a meta-analysis of randomized controlled trials.

PURPOSE: Vitamins and polyunsaturated fatty acids (PUFAs) have been studied extensively as safe and manageable nutrient interventions for mild cognitive impairment (MCI). The purpose of the current meta-analysis was to examine the effects of vitamins and PUFAs on cognition and to compare the effects of single and multiple nutrient subgroups in patients with MCI. METHODS: Randomized controlled trials (RCTs) written in English and Chinese were retrieved from eight databases, namely, PubMed, CENTRAL, Embase, CINAHL, Web of Science, SinoMed, CNKI, and Wanfang Data, from their respective dates of inception until 16 July 2023. The quality of the included studies was assessed using the Cochrane Risk of Bias Tool 2.0. Meta-analyses were performed to determine the standardized mean differences (SMDs) in global cognitive function, memory function, attention, visuospatial skills, executive function, and processing speed between the supplement and control groups using 95% confidence intervals (CI) and I2. Prospero registration number: CRD42021292360. RESULTS: Sixteen RCTs that studied different types of vitamins and PUFAs were included. The meta-analysis revealed that vitamins affected global cognitive function (SMD = 0.58, 95% CI = [0.20, 0.96], P = 0.003), memory function (SMD = 2.55, 95% CI = [1.01, 4.09], P = 0.001), and attention (SMD = 3.14, 95% CI = [1.00, 5.28], P = 0.004) in patients with MCI, and PUFAs showed effects on memory function (SMD = 0.65, 95% CI = [0.32, 0.99], P < 0.001) and attention (SMD = 2.98, 95% CI = [2.11, 3.84], P < 0.001). Single vitamin B (folic acid [FA]: SMD = 1.21, 95% CI = [0.87, 1.55]) supplementation may be more effective than multiple nutrients (FA and vitamin B12: SMD = 0.71, 95% CI = [0.41, 1.01]; and FA combined with docosahexaenoic acid [DHA]: SMD = 0.58, 95% CI = [0.34, 0.83]) in global cognitive function. CONCLUSIONS: FA, vitamin B6, vitamin B12, and vitamin D may improve global cognitive function, memory function, and attention in patients with MCI. Eicosapentaenoic acid (EPA) and DHA may improve memory function and attention. We also noted that FA may exert a greater effect than a vitamin B combination (FA and vitamin B12) or the combination of FA and DHA. However, because of the low evidence-based intensity, further trials are necessary to confirm these findings.

Research Progress on Cognitive Frailty in Older Adults with Chronic Kidney Disease.

BACKGROUND: As the medical challenges posed by the ageing population become increasingly severe, the proportion of older people among patients with chronic kidney disease (CKD) is increasing every year. SUMMARY: The prevalence of frailty in patients with CKD is significantly higher than that in the general population, and older patients are also a high-risk group for frailty and cognitive impairment. Cognitive frailty, as an important subtype of frailty, is a syndrome characterised by cognitive dysfunction caused by physiological factors, excluding Alzheimer's disease and other types of dementia. It is characterised by the coexistence of physical frailty and cognitive impairment. Previous studies have mainly focused on cognitive impairment, and there is limited research on cognitive frailty, particularly in older patients with CKD. KEY MESSAGES: This article provides a comprehensive review of the concept, epidemiology, screening methods, prevention, and treatment measures and possible pathogenesis of cognitive frailty in patients with CKD.

Circ-Luc7l Absence Attenuates Diabetic Nephropathy Progression by Reducing Mesangial Cell Excessive Proliferation, Inflammation, and Extracellular Matrix Accumulation via Mediating the miR-205-5p/Tgfbr1 Pathway.

Diabetic nephropathy (DN) threatens the survival quality of patients, with complex pathogenesis. Circular RNA (circRNA) dysregulation occurs in DN development. This work aimed to investigate the role of circ-Luc7l in DN cell models and related molecular mechanisms. The expression of circ-Luc7l, microRNA (miR)-205-5p, and transforming growth factor-beta receptor 1 (Tgfbr1) was examined by real-time quantitative PCR (RT-qPCR). Cell viability and proliferation were detected by Cell Counting Kit-8 (CCK-8) assay and EdU assay. The expression of extracellular matrix (ECM)-related markers and Tgrbr1 protein was measured by Western blot. The binding between miR-205-5p and circ-Luc7l or Tgfbr1 was validated by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay, or RNA pull-down assay. Experimental animal models were established to elucidate the function of circ-Luc7l in vivo. Circ-Luc7l expression was notably enhanced in high glucose (HG)-treated mesangial cells. Knockdown of circ-Luc7l attenuated HG-induced cell proliferation, inflammation, and ECM accumulation in vitro and relieved inflammation and ECM accumulation of kidneys of diabetic mice in vivo. Circ-Luc7l targeted miR-205-5p, and miR-205-5p inhibition rescued the depletion effects of circ-Luc7l knockdown on cell proliferation, inflammation, and ECM accumulation. MiR-205-5p bound to Tgfbr1 whose expression was negatively regulated by circ-Luc7l. Tgfbr1 overexpression also rescued the depletion effects of circ-Luc7l knockdown on cell proliferation, inflammation, and ECM accumulation. In HG conditions, increased circ-Luc7l upregulated Tgfbr1 expression via targeting miR-205-5p to induce DN progression.

Multi-Scale Attention Network for Building Extraction from High-Resolution Remote Sensing Images.

The precise building extraction from high-resolution remote sensing images holds significant application for urban planning, resource management, and environmental conservation. In recent years, deep neural networks (DNNs) have garnered substantial attention for their adeptness in learning and extracting features, becoming integral to building extraction methodologies and yielding noteworthy performance outcomes. Nonetheless, prevailing DNN-based models for building extraction often overlook spatial information during the feature extraction phase. Additionally, many existing models employ a simplistic and direct approach in the feature fusion stage, potentially leading to spurious target detection and the amplification of internal noise. To address these concerns, we present a multi-scale attention network (MSANet) tailored for building extraction from high-resolution remote sensing images. In our approach, we initially extracted multi-scale building feature information, leveraging the multi-scale channel attention mechanism and multi-scale spatial attention mechanism. Subsequently, we employed adaptive hierarchical weighting processes on the extracted building features. Concurrently, we introduced a gating mechanism to facilitate the effective fusion of multi-scale features. The efficacy of the proposed MSANet was evaluated using the WHU aerial image dataset and the WHU satellite image dataset. The experimental results demonstrate compelling performance metrics, with the F1 scores registering at 93.76% and 77.64% on the WHU aerial imagery dataset and WHU satellite dataset II, respectively. Furthermore, the intersection over union (IoU) values stood at 88.25% and 63.46%, surpassing benchmarks set by DeepLabV3 and GSMC.

Design and impact assessment of policies to overcome oversupply in China's national carbon market.

China has adopted a national carbon emissions trading market to promote emission reductions, but until now, overallocation of allowances suffer low carbon prices and thus to unfulfilled emission reduction goals. We report a general equilibrium modeling that indicates the flexible compliance and price adjustment mechanism of the carbon market, along with explores the solution to the oversupply of allowances in the China's national carbon market. We find that, under the current policy, the initial loose allowance allocation decreases the overall carbon price, and simultaneously the total amount of banked carbon allowances reaches 4.880 billion tons in 2030, resulting in the level of carbon price cannot achieve NDC (Nationally Determined Contribution) targets. However, by introducing carbon market price adjustment schemes, we observe that the cumulative amount of allowances can effectively reduce, enabling the carbon price rising. Importantly, the amount of the supply of allowances decreases most under the benchmark decrease scenario, which increases the emission reduction pressure of the enterprises from the beginning, leading to the largest economic losses, the price-based adjustment mechanism raises the carbon price to expected level at the minimize economic losses, and the quantity-based adjustment mechanism is more sensitive to policy parameters compared to the price -based adjustment mechanism. These findings offer a promising avenue for selecting cost-effective price adjustment mechanism to improve price mechanism design for national carbon markets.

Functional responses of two species of predatory mites (Acari: Phytoseiidae) to eggs and first-instar nymphs of Bactericera Gobica Logniova (Homoptera: Psyllidae).

The goji berry psyllid, Bactericera gobica Logniova (Homoptera: Psyllidae), is one of the most important pests on goji berry plants (Lycium barbarum L.), whose fruits are widely used in traditional Chinese medicine and food. However, chemical control is still the predominant control strategy of this pest. Recently, two species of predatory mites, Neoseiulus setarius Ma, Meng & Fan and Neoseiulus barkeri Hughes were found to be associated with B. gobica in China. To assess their predation potential against B. gobica, the functional responses of these two phytoseiid species feeding on different densities (2, 4, 8, 12, 16, 24 and 32 individuals) of B. gobica eggs and 1st instar nymphs were compared at a temperature of 25ºC ± 1º C. Logistic regression analysis revealed that both predatory mite species exhibited type Holling-II functional responses on eggs and 1st instar nymphs of B. gobica, with the predation number increased for both predators as the density of prey increased. Overall, N. setarius consumed more prey compared to N. barkeri across all levels of prey densities. Meanwhile, the highest attack rate (α = 0.0283), the lowest handling time (Th = 1.1324 h prey- 1), and the highest estimated maximum predation rate (T/Th = 21.19 prey day- 1) were all observed for N. setarius fed with 1st instar nymphs of B. gobica. These findings suggest that it is worthy considering utilizing N. setarius and N. barkeri as candidate biocontrol agents of B. gobica, with N. setarius appearing to be a more effective predator than N. barkeri.

[Effect of Using Hydrogen Peroxide for Periodic Disinfection Combined With Continuous Disinfection to Control Contamination in Dental Unit Waterline]. / è¿‡æ°§åŒ–æ°¢å®šæœŸæ¶ˆæ¯’ç»“åˆæŒç»­æ¶ˆæ¯’å¯¹å£è ”ç»¼åˆæ²»ç–—å°æ°´è·¯æ±¡æŸ“æŽ§åˆ¶çš„æœ‰æ•ˆæ€§è§‚å¯Ÿ.

Objective: To observe the effect of using hydrogen peroxide in periodic disinfection combining with continuous disinfection of dental unit waterlines and to provide references for the selection of waterway disinfection measures. Methods: A total of 4 dental units in a hospital of stomatology were selected through convenience sampling. The dental unit waterlines received periodic disinfection once every 4 weeks in addition to continuous disinfection (When the dental units were not used for more than 3 days, an additional periodic disinfection would be performed.). Periodic disinfection referred to filling up the waterlines with a disinfectant solution (1.4% hydrogen peroxide) by using the waterline disinfection device that came with the dental unit, immersing for 24 hours, and then emptying out the disinfectant solution. Continuous disinfection referred to using hydrogen peroxide at a concentration of 0.014% as dental treatment water and using it to flush the waterlines for 2 minutes before any dental treatment in the morning and to flush the waterlines for 30 seconds after each dental treatment. The study lasted for 25 weeks, with periodic disinfection being performed for 7 times and continuous disinfection carried out for the rest of the dental treatment time. During the 25 weeks, water samples were collected from air/water syringes and high-speed handpieces. Then, the water samples were incubated and the bacterial concentration and the qualification rates were calculated accordingly. When the bacterial concentration≤100 CFU/ mL, the water samples were considered to be qualified. Waterline tubes of 1 cm were collected before and after the 25 weeks of disinfection with hydrogen peroxide. Biofilms in the waterline tube were observed under scanning electron microscope. Results: A total of 352 water samples were collected. Eight water samples were collected before disinfection with hydrogen peroxide, with the median of bacterial concentration being 3140 CFU/mL. On the first day of disinfection with hydrogen peroxide, the median bacterial concentration in dental treatment water was 7.5 CFU/mL. There was a significant difference between the bacterial concentration of the water samples before the disinfection and that after the disinfection (P=0.012). A total of 344 water samples were collected after the disinfection, with the median bacterial concentrations for air/water syringes and high-speed handpieces being 11 CFU/mL and 11CFU/mL and the qualified rates being 83.7% and 82.0%, respectively. There was no significant difference in bacterial concentration or the qualification rates. During week 1 through week 9 of the disinfection, the qualification rates of the dental treatment water always exceeded 80% in 8 weeks, with week 3 being the exception. In the two four-week disinfection periods of week 14 through week 17 and week 18 through week 21, the qualification rate was maintained at above 80% for only the first two weeks and started to decrease from the third week. Biofilm morphology was observed under scanning electron microscope. Before the disinfection, the biofilm was found to be a dense structure and the mixture of a large number of bacteria. After 25 weeks of the disinfection, the biofilm structure appeared to be loose and did not show consistent characteristics of a large number of bacteria retained. Conclusion: Periodic disinfection combined with continuous disinfection using hydrogen peroxide can effectively control contamination in dental unit waterlines. But the cycles of periodic disinfection and the concentration of hydrogen peroxide for continuous disinfection should be further discussed according to the actual clinical situation.

Ultrasound imaging findings in primary biliary cholangitis.

BACKGROUND: Our study aimed to analyze the characteristics of ultrasound images corresponding to each histological stage of primary biliary cholangitis (PBC). METHODS: We prospectively analyzed 75 confirmed cases of PBC and used liver biopsy as the gold standard to determine the disease stage. RESULTS: The typical ultrasound images of patients with PBC were characterized by a thickening of the portal vein wall (PVW) and periportal hypoechoic band (PHB) width with increasing histological stages, and significant increases in the left hepatic lobe diameter (LHLD) in stage II (by 64.0%) and stage III (by 69.2%). PHB width (r = 0.857, p < 0.001), PVW thickness (r = 0.488, p < 0.001), and spleen area (r = 0.8774, p < 0.001) were positively correlated with the histological stage. Significant changes were noted in the liver surface, echo texture, and edge between different stages. The areas under the receiver operating characteristic curve of composite indicators were 0.965 for predicting progressive PBC(≥ stage 2), and 0.926 for predicting advanced PBC(≥ stage 3). CONCLUSIONS: The ultrasound imaging characteristics of patients with PBC varied according to the histological staging. LHLD, PVW thickness, and PHB width were significantly correlated with the histological stage. A combination of high- and low-frequency ultrasound imaging can provide relevant cues regarding the degree of PBC progression and important clinical reference values. The application of all the ultrasound image findings as the composite indicators can better predict progressive and advanced PBC, providing important clinical reference values.

Adverse effects of unilateral transfemoral amputation on para-alpine sit skiers and mitigation methods.

OBJECTIVES: This study aimed to evaluate the adverse effects of unilateral transfemoral amputation on neuromuscular and kinematic parameters in alpine sit skiers, and to determine if additional restraints on the human-bucket interface could help mitigate the effects. DESIGN: Cross-sectional, repeated measures study. METHODS: Simulated skiing tests were conducted indoors involving 10 skiers with unilateral transfemoral amputation and 10 able-bodied participants. A Paralympic silver medalist performed slalom skiing tests on snow. These tests were conducted with and without additional strapping on the residual limb. Surface electromyography of trunk muscles and athletic performance was measured, and the asymmetry index was calculated. RESULTS: Athletes were significantly dependent on muscle activation on the dominant side (asymmetry index = 7.8 %-28.3 %, p < 0.05). Worse athletic performance to the dominant side was found based on inclination angles of the indoor board (asymmetry index = -9.8 %, p = 0.014) and outdoor sit ski (-11.1 %, p = 0.006), and distance to the gate poles during skiing turns (18.6 %, p < 0.001). After using additional restraints, the above asymmetry index declined significantly (asymmetry index < 4.5 %, p < 0.05). Furthermore, athletic performance was significantly improved on both body sides by 11.1 %-30.7 % (p < 0.05). CONCLUSIONS: Unilateral transfemoral amputation caused the dependence on the trunk muscles of the dominant side and the corresponding unilateral poor performance in athletes. Adjusting restraints in the human-equipment interface by additional strapping could mitigate the asymmetry issues and improve athletic performance.

A sodium alginate - silk fibroin biosponge loaded with thrombin: Effective hemostasis and wound healing.

In trauma first aid, rapid hemostasis is a priority, extricating patients from hemorrhagic shock and infection risks. This paper explores novel hemostatic materials, using ion-crosslinking and freeze-drying techniques. Iterative experiments determined optimal conditions for the temperature-variable mixing-freeze-drying chemical reaction of sodium alginate (SA)/silk fibroin (SF). We used SA, SA/SF, SA/SF-TB and commercial hemostatic sponge control samples to perform hemostasis experiments on rat liver injury and femoral artery injury models, and to perform wound healing experiments on rat back full-layer skin. The results showed that the hemostatic time and blood loss of SA/SF-TB group rats (liver hemorrhage model: 397.17 ± 34.80 mg, 77.83 ± 7.41 s; Femoral artery bleeding model: 940.33 ± 41.93 mg, 96.83 ± 4.07 s) was significantly better than other experimental groups, and similar to the commercial group. The wound healing experiment showed that the new granulation tissue thickness of SA/SF-TB group was thicker (380.39 ± 28.56 µm) at day 14. In addition, the material properties and biocompatibility of sponges were characterized by cell experiments and in vivo embedding experiments. All the results showed that the SA/SF-TB hemostatic sponge prepared in this study could not only seal the wound quickly and stop bleeding, but also promote the growth of epidermal cells and fibroblasts and accelerate wound healing. This new material solves the shortcomings of traditional materials such as low stability, limited shelf life, high unit price, and has good biocompatibility, easy preparation, rapid hemostasis and other excellent properties. Therefore, this innovative hemostatic material has great prospects and potential in clinical applications.

Baicalein exerts beneficial effects in lipopolysaccharide-induced pulmonary inflammation by modulating macrophage polarization and inhibiting pyroptosis.

The disruption of the immune system by viral attack is a major influencing factor in the lethality of COVID-19. Baicalein is one of the key effective compounds against COVID-19. The molecular mechanisms regarding the anti-inflammatory properties of Baicalein are still unclear. In this study, we established LPS-induced mice to elucidate the role of Baicalein in the treatment of acute lung injury (ALI) and its potential molecular mechanisms. In vivo experiments showed that Baicalein could significantly ameliorate LPS-induced acute lung injury and reduce proteinous edema in lung tissue. In addition, Baicalein inhibited M1 macrophage polarization, promote M2 macrophage polarization, and regulate inflammatory responses. Furthermore, Baicalein could inhibit the expression of protein molecules associated with pyroptosis and mitigate the lung tissue injury. In summary, we revealed the therapeutic effects of Baicalein in acute lung injury, providing the theoretical basis for its clinical application.

A multi-scale feature fusion neural network for multi-class disease classification on the maize leaf images.

Maize is a globally important cereal crop, however, maize leaf disease is one of the most common and devastating diseases that afflict it. Artificial intelligence methods face challenges in identifying and classifying maize leaf diseases due to variations in image quality, similarity among diseases, disease severity, limited dataset availability, and limited interpretability. To address these challenges, we propose a residual-based multi-scale network (MResNet) for classifying multi-type maize leaf diseases from maize images. MResNet consists of two residual subnets with different scales, enabling the model to detect diseases in maize leaf images at different scales. We further utilize a hybrid feature weight optimization method to optimize and fuse the feature mapping weights of two subnets. We validate MResNet on a maize leaf diseases dataset. MResNet achieves 97.45% accuracy. The performance of MResNet surpasses other state-of-the-art methods. Various experiments and two additional datasets confirm the generalization performance of our model. Furthermore, thermodynamic diagram analysis increases the interpretability of the model. This study provides technical support for the disease classification of agricultural plants.

Smoking behavior associated upregulation of SERPINB12 promotes proliferation and metastasis via activating WNT signaling in NSCLC.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of morality among all malignant tumors. Smoking is one of the most important causes of NSCLC, which contributes not only to the initiation of NSCLC but also to its progression. The identification of specific biomarkers associated with smoking will promote diagnosis and treatment. METHODS: Data mining was used to identify the smoking associated gene SERPINB12. CCK8 assays, colony formation assays, a mouse xenograft model and transwell assays were performed to measure the biological functions of SERPINB12 in NSCLC. GSEA, luciferase reporter assays and immunofluorescence were conducted to explore the potential molecular mechanisms of SERPINB12 in NSCLC. RESULTS: In this study, by data mining the TCGA database, we found that SERPINB12 was greatly upregulated in NSCLC patients with cigarette consumption behavior, while the expression level was positively correlated with disease grade and poor prognosis. SERPINB12 is a kind of serpin peptidase inhibitor, but its function in malignant tumors remains largely unknown. Functionally, knockdown of SERPINB12 observably inhibited the proliferation and metastasis of NSCLC cells in vitro and in vivo. Moreover, downregulation of SERPINB12 attenuated Wnt signaling by inhibiting the nuclear translocation of ß-catenin, which explained the molecular mechanism underlying tumor progression. CONCLUSIONS: In conclusion, SERPINB12 functions as a tumorigenesis factor, which could be a promising biomarker for NSCLC patients with smoking behavior, as well as a therapeutic target.

Role and regulation of FOXO3a: new insights into breast cancer therapy.

Breast cancer is the most common malignancy in the world, particularly affecting female cancer patients. Enhancing the therapeutic strategies for breast cancer necessitates identifying molecular drug targets that effectively eliminate tumor cells. One of these prominent targets is the forkhead and O3a class (FOXO3a), a member of the forkhead transcription factor subfamily. FOXO3a plays a pivotal role in various cellular processes, including apoptosis, proliferation, cell cycle regulation, and drug resistance. It acts as a tumor suppressor in multiple cancer types, although its specific role in cancer remains unclear. Moreover, FOXO3a shows promise as a potential marker for tumor diagnosis and prognosis in breast cancer patients. In addition, it is actively influenced by common anti-breast cancer drugs like paclitaxel, simvastatin, and gefitinib. In breast cancer, the regulation of FOXO3a involves intricate networks, encompassing post-translational modification post-translational regulation by non-coding RNA (ncRNA) and protein-protein interaction. The specific mechanism of FOXO3a in breast cancer urgently requires further investigation. This review aims to systematically elucidate the role of FOXO3a in breast cancer. Additionally, it reviews the interaction of FOXO3a and its upstream and downstream signaling pathway-related molecules to uncover potential therapeutic drugs and related regulatory factors for breast cancer treatment by regulating FOXO3a.