Smurf1 polyubiquitinates on K285/K282 of the kinases Mst1/2 to attenuate their tumor-suppressor functions.

Sterile 20-like kinases Mst1 and Mst2 (Mst1/2) and large tumor suppressor 1/2 are core kinases to mediate Hippo signaling in maintaining tissue homeostasis. We have previously demonstrated that Smad ubiquitin (Ub) regulatory factor 1 (Smurf1), a HECT-type E3 ligase, ubiquitinates and in turn destabilizes large tumor suppressor 1/2 to induce the transcriptional output of Hippo signaling. Here, we unexpectedly find that Smurf1 interacts with and polyubiquitinates Mst1/2 by virtue of K27- and K29-linked Ub chains, resulting in the proteasomal degradation of Mst1/2 and attenuation of their tumor-suppressor functions. Among the potential Ub acceptor sites on Mst1/2, K285/K282 are conserved and essential for Smurf1-induced polyubiquitination and degradation of Mst1/2 as well as transcriptional output of Hippo signaling. As a result, K285R/K282R mutation of Mst1/2 not only negates the transcriptional output of Hippo signaling but enhances the tumor-suppressor functions of Mst1/2. Together, we demonstrate that Smurf1-mediated polyubiquitination on K285/K282 of Mst1/2 destabilizes Mst1/2 to attenuate their tumor-suppressor functions. Thus, the present study identifies Smurf1-mediated ubiquitination of Mst1/2 as a hitherto uncharacterized mechanism fine-tuning the Hippo signaling pathway and may provide additional targets for therapeutic intervention of diseases associated with this important pathway.

Detection of peach soluble solids based on near-infrared spectroscopy with High Order Spatial Interaction network.

BACKGROUND: Due to the scalability of deep learning technology, researchers have applied it to the non-destructive testing of peach internal quality. In addition, the soluble solids content (SSC) is an important internal quality indicator that determines the quality of peaches. Peaches with high SSC have a sweeter taste and better texture, making them popular in the market. Therefore, SSC is an important indicator for measuring peach internal quality and making harvesting decisions. RESULTS: This article presents the High Order Spatial Interaction Network (HOSINet), which combines the Position Attention Module (PAM) and Channel Attention Module (CAM). Additionally, a feature wavelength selection algorithm similar to the Group-based Clustering Subspace Representation (GCSR-C) is used to establish the Position and Channel Attention Module-High Order Spatial Interaction (PC-HOSI) model for peach SSC prediction. The accuracy of this model is compared with traditional machine learning and traditional deep learning models. Finally, the permutation algorithm is combined with deep learning models to visually evaluate the importance of feature wavelengths. Increasing the order of the PC-HOSI model enhances its ability to learn spatial correlations in the dataset, thus improving its predictive performance. CONCLUSION: The optimal model, PC-HOSI model, performed well with an order of 3 (PC-HOSI-3), with a root mean square error of 0.421 °Brix and a coefficient of determination of 0.864. Compared with traditional machine learning and deep learning algorithms, the coefficient of determination for the prediction set was improved by 0.07 and 0.39, respectively. The permutation algorithm also provided interpretability analysis for the predictions of the deep learning model, offering insights into the importance of spectral bands. These results contribute to the accurate prediction of SSC in peaches and support research on interpretability of neural network models for prediction. © 2024 Society of Chemical Industry.

Cordycepin: A review of strategies to improve the bioavailability and efficacy.

Cordycepin is a bioactive compound extracted from Cordyceps militaris. As a natural antibiotic, cordycepin has a wide variety of pharmacological effects. Unfortunately, this highly effective natural antibiotic is proved to undergo rapid deamination by adenosine deaminase (ADA) in vivo and, as a consequence, its half-life is shortened and bioavailability is decreased. Therefore, it is of critical importance to work out ways to slow down the deamination so as to increase its bioavailability and efficacy. This study reviews recent researches on a series of aspects of cordycepin such as the bioactive molecule's pharmacological action, metabolism and transformation as well as the underlying mechanism, pharmacokinetics and, particularly, the methods for reducing the degradation to improve the bioavailability and efficacy. It is drawn that there are three methods that can be applied to improve the bioavailability and efficacy: to co-administrate an ADA inhibitor and cordycepin, to develop more effective derivatives via structural modification, and to apply new drug delivery systems. The new knowledge can help optimize the application of the highly potent natural antibiotic-cordycepin and develop novel therapeutic strategies.

Insight into the Fe-Ni/biochar composite supported three-dimensional electro-Fenton removal of electronic industry wastewater.

For the efficient removal of the bio-refractory organic pollutants in the electronic industry wastewater, the Ni-Fe (oxides) modified three-dimension (3D) particle electrode was applied in electro-Fenton system (3D/EF), where iron ions were released from anode and deposited onto algal biochar (ABC) to prepare composite catalyst during reaction process. Firstly, scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and Brunauer-Emmett-Teller (BET) analysis were applied to confirm successful fabrication of the 3D particle electrode materials. Secondly, COD removal efficiency could reach about 80%, which was about 20% higher than that in 2D/EF system, under the optimized conditions as 2.0 g/L of Ni-ABC particle electrodes, initial pH of 3, 100 mL/min of aeration intensity and 20 mA/cm2 of applied current density. Thirdly, characterized using three-dimensional fluorescence spectroscopy and GC-MS analysis, it seemed that most of the macromolecular substances could be degraded, whereas mono-2-ethylhexyl phthalate (MEHP) was identified as the most abundant and representative compound. Finally, possible degradation pathway of MEHP in 3D/EF system was proposed including dealkylation, cleavage of C-O bond, and demethylation. Therefore, this study provides a new strategy in designing EF system employing bimetal doped biochar composite for an efficient elimination of organic pollutants within electronic industry wastewater.

Global Cellular Metabolic Rewiring Adapts Corynebacterium glutamicum to Efficient Nonnatural Xylose Utilization.

Xylose, the major component of lignocellulosic biomass, cannot be naturally or efficiently utilized by most microorganisms. Xylose (co)utilization is considered a cornerstone of efficient lignocellulose-based biomanufacturing. We evolved a rapidly xylose-utilizing strain, Cev2-18-5, which showed the highest reported specific growth rate (0.357 h-1) on xylose among plasmid-free Corynebacterium glutamicum strains. A genetically clear chassis strain, CGS15, was correspondingly reconstructed with an efficient glucose-xylose coutilization performance based on comparative genomic analysis and mutation reconstruction. With the introduction of a succinate-producing plasmid, the resulting strain, CGS15-SA1, can efficiently produce 97.1 g/L of succinate with an average productivity of 8.09 g/L/h by simultaneously utilizing glucose and xylose from corn stalk hydrolysate. We further revealed a novel xylose regulatory mechanism mediated by the endogenous transcription factor IpsA with global regulatory effects on C. glutamicum. A synergistic effect on carbon metabolism and energy supply, motivated by three genomic mutations (Psod(C131T)-xylAB, Ptuf(Δ21)-araE, and ipsAC331T), was found to endow C. glutamicum with the efficient xylose utilization and rapid growth phenotype. Overall, this work not only provides promising C. glutamicum chassis strains for a lignocellulosic biorefinery but also enriches the understanding of the xylose regulatory mechanism. IMPORTANCE A novel xylose regulatory mechanism mediated by the transcription factor IpsA was revealed. A synergistic effect on carbon metabolism and energy supply was found to endow C. glutamicum with the efficient xylose utilization and rapid growth phenotype. The new xylose regulatory mechanism enriches the understanding of nonnatural substrate metabolism and encourages exploration new engineering targets for rapid xylose utilization. This work also provides a paradigm to understand and engineer the metabolism of nonnatural renewable substrates for sustainable biomanufacturing.

Proton-Promoted Nickel-Catalyzed Asymmetric Hydrogenation of Aliphatic Ketoacids.

A robust and highly active homogeneous chiral nickel-phosphine complex for the asymmetric hydrogenation of aliphatic γ- and δ-ketoacids has been discovered. The hydrogenation could proceed smoothly in the presence of 0.0133 mol% catalyst loading (S/C=7500). The coordination chemistry and catalytic behavior of Ni(OTf)2 with (S,S)-Ph-BPE were explored by 1 H NMR and HRMS. The mechanistic studies revealed that a proton promoted the activation of the substrate C=O bond and controlled the stereoselectivity through hydrogen bonds. A series of chiral γ- and δ-alkyl substituted lactones were obtained in high yields with excellent enantioselectivities (up to 98 % yield and 99 % ee). In addition, this catalytic system also demonstrated that levulinic acid produced from a biomass feedstock was converted into chiral γ-valerolactone without loss of ee value.

Enhancement of scutellarin oral delivery efficacy by vitamin B12-modified amphiphilic chitosan derivatives to treat type II diabetes induced-retinopathy.

BACKGROUND: Diabetic retinopathy is the most common complication in diabetic patients relates to high expression of VEGF and microaneurysms. Scutellarin (Scu) turned out to be effective against diabetes related vascular endothelial cell dysfunction. However, its clinical applications have been limited by its low bioavailability. In this study, we formulated and characterized a novel intestinal target nanoparticle carrier based on amphiphilic chitosan derivatives (Chit-DC-VB12) loaded with scutellarin to enhance its bioavailability and then evaluated its therapeutic effect in experimental diabetic retinopathy model. RESULTS: Chit-DC-VB12 nanoparticles showed low toxicity toward the human colon adenocarcinoma (Caco-2) cells and zebra fish within concentration of 250 µg/ml, owing to good biocompatibility of chitosan. The scutellarin-loaded Chit-DC-VB12 nanoparticles (Chit-DC-VB12-Scu) were then prepared by self-assembly in aqueous solution. Scanning electron microscopy and dynamic light scattering analysis indicated that the Chit-DC-VB12-Scu nanoparticles were spherical particles in the sizes ranging from 150 to 250 nm. The Chit-DC-VB12-Scu nanoparticles exhibited high permeation in Caco-2 cell, indicated it could be beneficial to be absorbed in humans. We also found that Chit-DC-VB12 nanoparticles had a high cellular uptake. Bioavailability studies were performed in Sprague-Dawley rats, which present the area under the curve of scutellarin of Chit-DC-VB12-Scu was two to threefolds greater than that of free scutellarin alone. Further to assess the therapeutic efficacy of diabetic retinopathy, we showed Chit-DC-VB12-Scu down-regulated central retinal artery resistivity index and the expression of angiogenesis proteins (VEGF, VEGFR2, and vWF) of retinas in type II diabetic rats. CONCLUSIONS: Chit-DC-VB12 nanoparticles loaded with scutellarin have better bioavailability and cellular uptake efficiency than Scu, while Chit-DC-VB12-Scu nanoparticles alleviated the structural disorder of intraretinal neovessels in the retina induced by diabetes, and it also inhibited the retinal neovascularization via down-regulated the expression of angiogenesis proteins. In conclusion, the Chit-DC-VB12 nanoparticles enhanced scutellarin oral delivery efficacy and exhibited potential as small intestinal target promising nano-carriers for treatment of type II diabetes induced-retinopathy.

Research on emergency scheduling based on improved genetic algorithm in harvester failure scenarios.

In response to the issue of harvesting machine failures affecting crop harvesting timing, this study develops an emergency scheduling model and proposes a hybrid optimization algorithm that combines a genetic algorithm and an ant colony algorithm. By enhancing the genetic algorithm's crossover and mutation methods and incorporating the ant colony algorithm, the proposed algorithm can prevent local optima, thus minimizing disruptions to the overall scheduling plan. Field data from Deyang, Sichuan Province, were utilized, and simulations on various harvesting machines experiencing random faults were conducted. Results indicated that the improved genetic algorithm reduced the optimal comprehensive scheduling cost during random fault occurrences by 47.49%, 19.60%, and 32.45% compared to the basic genetic algorithm and by 34.70%, 14.80%, and 24.40% compared to the ant colony algorithm. The improved algorithm showcases robust global optimization capabilities, high stability, and rapid convergence, offering effective emergency scheduling solutions in case of harvesting machine failures. Furthermore, a visual management system for agricultural machinery scheduling was developed to provide software support for optimizing agricultural machinery scheduling.

Hyperspectral Imaging Using a Convolutional Neural Network with Transformer for the Soluble Solid Content and pH Prediction of Cherry Tomatoes.

Cherry tomatoes are cultivated worldwide and favored by consumers of different ages. The soluble solid content (SSC) and pH are two of the most important quality attributes of cherry tomatoes. The rapid and non-destructive measurement of the SSC and pH of cherry tomatoes is of great significance to their production and consumption. In this research, hyperspectral imaging combined with a convolutional neural network with Transformer (CNN-Transformer) was utilized to analyze the SSC and pH of cherry tomatoes. Conventional machine learning and deep learning models were established for the determination of the SSC and pH. The findings demonstrated that CNN-Transformer yielded outstanding results in predicting the SSC, with the coefficient of determination of calibration (R2C), validation (R2V), and prediction (R2P) for the SSC being 0.83, 0.87, and 0.83, respectively. Relatively worse results were obtained for the pH value prediction, with R2C, R2V, and R2P values of 0.74, 0.68, and 0.60, respectively. Furthermore, the visualization of the CNN-Transformer model revealed the wavelength weight distributions, indicating that the 1380-1650 nm range served as the characteristic band for the SSC, while the spectral range at 945-1280 nm was the characteristic band for pH. In conclusion, integrating spectral information features with the attention mechanism of Transformer through a convolutional neural network can enhance the accuracy of predicting the SSC and pH for cherry tomatoes.

Relationship of sleep with diurnal cortisol rhythm considering sleep measurement and cortisol sampling schemes.

Information on the relationships between the previous night's sleep and the next-day diurnal cortisol rhythm is inconsistent due to confounding factors such as sleep measurements (trait/state sleep and objective/subjective sleep) and cortisol sampling schemes. Therefore, this study aimed to investigate these relationships, considering the confounding factors. College students (n = 79) wore actigraphy for 3 days to undergo an evaluation of previous night-time sleep objectively and reported their subjective sleep parameters in a sleep diary. In addition, participants provided six salivary cortisol samples daily. Furthermore, six cortisol sampling schemes were created to reflect diurnal cortisol rhythms, and two different methods were used to calculate the index of diurnal cortisol slope (DCS). A multilevel model was created to examine the impact of both trait and state sleep on next-day diurnal cortisol rhythm. The results revealed that higher objective state sleep efficiency and longer objective state total sleep time were associated with a higher cortisol awakening response (CAR). Moreover, higher objective trait sleep efficiency and longer objective trait total sleep time were associated with higher waking cortisol levels and steeper DCS. In addition, a minimum of four saliva samples were required at different time points, including upon waking, 30 min after waking, 1 h after waking, and at bedtime, to explore the relationship of sleep efficiency/total sleep time with waking cortisol, CAR, and DCS. Furthermore, the index of the peak-to-bed slope was appropriately employed to examine the relationship between sleep efficiency and DCS, whereas the wake-to-bed slope was effective for examining the relationship between total sleep time and DCS. In summary, this study clarified the relationship between sleep and next-day diurnal cortisol rhythm and suggested a cost-effective cortisol sampling schedule and calculation methods.

Ganoderic Acid A: A Potential Natural Neuroprotective Agent for Neurological Disorders: A Review.

Ganoderic acid A (GAA) is one of the major triterpenoids in Ganoderma lucidum (GL). Accumulating evidence has indicated that GAA demonstrates multiple pharmacological effects and exhibits treatment potential for various neurological disorders. Here, the effects and mechanisms of GAA in the treatment of neurological disorders were evaluated and discussed through previous research results. By summarizing previous research results, we found that GAA may play a neuroprotective role through various mechanisms: anti-inflammatory, anti-oxidative stress, anti-apoptosis, protection of nerve cells, and regulation of nerve growth factor. Therefore, GAA is a promising natural neuroprotective agent and this review would contribute to the future development of GAA as a novel clinical candidate drug for treating neurological diseases.

A review of the phosphorus removal of polyphosphate-accumulating organisms in natural and engineered systems.

Increasing eutrophication has led to a continuous deterioration of many aquatic ecosystems. Polyphosphate-accumulating organisms (PAOs) can provide insight into the human response to this challenge, as they initiate enhanced biological phosphorus removal (EBPR) through cyclical anaerobic phosphorus release and aerobic phosphorus uptake. Although the limiting environmental factors for PAO growth and phosphorus removal have been widely discussed, there remains a gap in the knowledge surrounding the differences in the type and phosphorus removal efficiencies of natural and engineered PAO systems. Furthermore, due to the limitations of PAOs in conventional wastewater treatment environments, there is an urgent need to find functional PAOs in extreme environments for better wastewater treatment. Therefore, it is necessary to explore the effects of extreme conditions on the phosphorus removal efficiency of PAOs as well as the types, sources, and characteristics of PAOs. In this paper, we summarize the response mechanisms of PAOs, denitrifying polyphosphate-accumulating organisms (D-PAOs), aerobic denitrifying polyphosphate-accumulating organisms (AD-PAOs), and sulfur-related PAOs (S-PAOs). The mechanism of nitrogen and phosphorus removal in PAOs is related to the coupling cycles of carbon, nitrogen, phosphorus, and sulfur. The genera of PAOs differ in natural and engineered systems, but PAOs have more diversity in aquatic environments and soils. Recent studies on the impact of several parameters (e.g., temperature, carbon source, pH, and dissolved oxygen) and extracellular polymer substances on the phosphorus removal efficiency of PAOs in natural and engineered systems are further discussed. Most of the PAOs screened under extreme conditions still had high phosphorus removal efficiencies (>80.0 %). These results provide a reference for searching for PAOs with different adaptations to achieve better wastewater treatment.

Multi-omics and single cell characterization of cancer immunosenescence landscape.

Cellular senescence (CS) is closely related to tumor progression. However, the studies about CS genes across human cancers have not explored the relationship between cancer senescence signature and telomere length. Additionally, single-cell analyses have not revealed the evolutionary trends of malignant cells and immune cells at the CS level. We defined a CS-associated signature, called "senescence signature", and found that patients with higher senescence signature had worse prognosis. Higher senescence signature was related to older age, higher genomic instability, longer telomeres, increased lymphocytic infiltration, higher pro-tumor immune infiltrates (Treg cells and MDSCs), and could predict responses to immune checkpoint inhibitor therapy. Single-cell analysis further reveals malignant cells and immune cells share a consistent evolutionary trend at the CS level. MAPK signaling pathway and apoptotic processes may play a key role in CS, and senescence signature may effectively predict sensitivity of MEK1/2 inhibitors, ERK1/2 inhibitors and BCL-2 family inhibitors. We also developed a new CS prediction model of cancer survival and established a portal website to apply this model ( https://bio-pub.shinyapps.io/cs_nomo/ ).

Recycling utilization of Chinese medicine herbal residues resources: systematic evaluation on industrializable treatment modes.

Traditional Chinese medicine (TCM) is an indispensable part of the world health and medical system and plays an important role in treatment, prevention, and health care. These TCM produce a large amount of Chinese medicine herbal residues (CHMRs) during the application process, most of which are the residues after the decoction or extraction of botanical medicines. These CMHRs contain a large number of unused components, which can be used in medical, breeding, planting, materials, and other industries. Considering the practical application requirements, this paper mainly introduces the low-cost treatment methods of CHMRs, including the extraction of active ingredients, cultivation of edible fungi, and manufacture of feed. These methods not only have low upfront investment, but also have some income in the future. Furthermore, other methods are briefly introduced. In conclusion, this paper can provide a reference for people who need to deal with CMHRs and contribute to the sustainable development of TCM.

Girls Tolerate Girls, men condemn men: Gender differences in the impact of beautification strategies on trustworthiness and morality evaluation.

It's not just women who aspire to enhance their appearance; it's a universal human desire. An increasing number of men are gradually embracing beautification strategies as well. The impact of gender on perceptions of strategies users remains uncertain. This study focuses on the role of gender in beautification strategies and their influence on trustworthiness and morality evaluations. It aims to analyze the role played by both the gender of evaluators and the gender of targets, while also comparing the differences between the two most popular beautification strategies, makeup and cosmetic surgery, in shaping trustworthiness and morality evaluations. The results revealed male participants demonstrated a stronger negative bias towards these users, particularly male users. On the other hand, the research revealed that females exhibited greater tolerance when evaluating same-sex makeup users. Conversely, males gave more negative evaluations to same-sex strategies users. Furthermore, the results showed morality and trustworthiness evaluation for beautification targets was predicted by evaluators' acceptance of cosmetic surgery. This study not only contributes to the existing literature on gender differences in beautification strategies but also offers a gender-based perspective to help reduce the stigma associated with these strategies.

Advances in Mechanism and Application of Molecular Breeding of Medicinal Mushrooms: A Review.

With the development of molecular biology and genomics technology, mushroom breeding methods have changed from single traditional breeding to molecular breeding. Compared with traditional breeding methods, molecular breeding has the advantages of short time and high efficiency. It breaks through the restrictive factors of conventional breeding and improves the accuracy of breeding. Molecular breeding technology is gradually applied to mushroom breeding. This paper summarizes the concept of molecular breeding and the application progress of various molecular breeding technologies in mushroom breeding, in order to provide reference for future research on mushroom breeding.

Role of hippocampus and orbitofrontal cortex in the association of interdependent self-construal with an acute stress response.

Empirical evidence indicates that high interdependent self-construal (InterSC) is correlated with exaggerated acute stress responses; however, the underlying neural correlates remain unclear. Considering the regulatory effect of the prefrontal cortex and limbic system on the acute stress response, the primary aim of this study was to investigate the role of the orbitofrontal cortex (OFC) and hippocampus (HIP) in the relationship between InterSC and acute stress responses. Forty-eight healthy college students underwent a modified version of the Montreal imaging stress task (MIST), while brain activity was recorded using functional magnetic resonance imaging (fMRI). Participants' saliva samples and subjective stress feelings were collected before, during, and after the MIST. Additionally, participants' self-construal was measured using questionnaires. Results revealed that InterSC was positively correlated with the activation of OFC, which, in turn, was associated with higher subjective stress feelings. A higher InterSC was also significantly associated with an enhanced salivary cortisol response in those with lower HIP activity. Furthermore, the HIP moderated the indirect effect of InterSC on subjective stress feelings by moderating the effect of InterSC on neural activity in the OFC. This indicated the mediation of the OFC was stronger in those with higher neural activity in the HIP than in those with lower activity in the HIP. In summary, the current study proposed an important role of the OFC-HIP regions in the relationship between InterSC and acute stress responses, making contribution to broadening the field of personality and stress and deepening our understanding of individual differences in acute stress responses.

Hair Cortisone Predicts Lower Stress-induced Salivary Cortisol Response: Resting-state Functional Connectivity Between Salience and Limbic Networks.

Previous studies revealed that high long-term hypothalamic-pituitaryadrenal (HPA) axis activity measured by the hair cortisol concentrations predicts lower acute stress cortisol response and reported the influences of hair cortisol on brain activity during acute stress exposure. However, considering that long-term HPA axis activity has a close relationship with the brain's resting-state functional connectivity (RSFC), the current study aimed to explore the role of RSFC between limbic and salience network in this relationship. Seventy-seven healthy participants underwent resting-state imaging scans before performing the acute ScanSTRESS task. Saliva samples were collected to assess the levels of acute stress salivary cortisol. Hair samples were also collected, and the corticosteroid concentration extracted from these samples were used as a biomarker of long-term HPA axis activity. High hair cortisone (HairE) levels predicted lower acute stress cortisol response. Moreover, high HairE levels were significantly correlated with enhanced RSFC between limbic and salience networks, while RSFC was negatively associated with acute stress cortisol response. Importantly, the RSFC between left insula and left parahippocampus mediated the association between HairE and acute cortisol stress response. Taken together, this study uncovers the important role of RSFC between salience and limbic networks in the long-term relationship between HairE and acute cortisol response and contributes to a deeper understanding of the individual differences in acute stress response.

[Characteristics and Ecological Risk Assessment of Pharmaceutical Active Compounds in Guangdong Province].

Pharmaceutically active compounds(PhACs) have become a class of new pollutants in the environment after extensive production and use of PhACs in China. To investigate the pollution characteristics of PhACs in Guangdong Province, raw sewage was collected from 186 sewage treatment plants in 21 cities, including 178 townships and administrative districts in Guangdong Province. The pollution levels of ten typical PhACs in influent water of sewage treatment plants were analyzed using automatic solid phase extraction and high performance liquid chromatography-triple quadrupole mass spectrometry. The spatial distribution characteristics of PhACs in Guangdong Province were fully revealed, and the potential ecological risks of PhACs were evaluated. The results showed that PhACs were detected in all wastewater plants, and the mass concentration of PhACs ranged from 21.00 to 9558.25 ng·L-1. Metoprolo, acetaminophen, bezafibrate, and caffeine were the main pollutants. In terms of spatial distribution, the average mass concentration of ΣPhACs in various regions of Guangdong Province was in the following order:Pearl River Delta>North Guangdong>East Guangdong≈West Guangdong. When the mass concentration of ΣPhACs was over 2500 ng·L-1 in the influent water of sewage treatment plants, the concentration of PhACs in effluent was estimated according to the sewage disposal technology. The ecological risk of PhACs was carried out based on the effluent. The results revealed that the ecological risk of PhACs was low in Guangdong Province, and the risk of bezafibrate was moderate in the cities of Shaoguan, Jiangmen, and Shenzhen. The highest ecological risk of ΣPhACs was located in Shaoguan.

Sonic hedgehog signaling: Alternative splicing and pathogenic role in medulloblastoma.

Alternative splicing (AS) produces the different mRNA splicing bodies, which are then translated into multiple protein isoforms and participate in various biological functions. With a deeper understanding of alternative splicing through the study of transcriptomes using high-throughput sequencing-based methods, the correlation between aberrant AS and diseases triggered a great concern, especially abnormal AS and cancer. Medulloblastoma (MB) is an intracranial tumor in children. Sonic hedgehog MB (SHH-MB) accounted for approximately 30% of MB, which is associated with the activation of SHH signaling. Growing evidence shows that aberrant AS is closely related to the tumorigenesis of MB. Here, we briefly introduced the AS and its mechanism. Next, we described canonical/noncanonical hedgehog signaling and its correlation with MB. The main description focused on AS of various regulators in canonical hedgehog signaling in MB. In addition, we also described AS of various regulators in noncanonical hedgehog signaling. Meanwhile, activated hedgehog signaling also induces AS in MB. Then, we pointed out that aberrant AS of hedgehog signaling is associated with different MB subgroups. Finally, we summarized the therapeutic applications of targeted AS in cancer treatment. In summary, further understanding of AS in SHH-MB could develop therapeutic targets for splicing factors which may be a novel therapeutic strategy.