SUSD2 suppresses CD8+ T cell antitumor immunity by targeting IL-2 receptor signaling.

Dysfunctional CD8+ T cells, which have defective production of antitumor effectors, represent a major mediator of immunosuppression in the tumor microenvironment. Here, we show that SUSD2 is a negative regulator of CD8+ T cell antitumor function. Susd2-/- effector CD8+ T cells showed enhanced production of antitumor molecules, which consequently blunted tumor growth in multiple syngeneic mouse tumor models. Through a quantitative mass spectrometry assay, we found that SUSD2 interacted with interleukin (IL)-2 receptor α through sushi domain-dependent protein interactions and that this interaction suppressed the binding of IL-2, an essential cytokine for the effector functions of CD8+ T cells, to IL-2 receptor α. SUSD2 was not expressed on regulatory CD4+ T cells and did not affect the inhibitory function of these cells. Adoptive transfer of Susd2-/- chimeric antigen receptor T cells induced a robust antitumor response in mice, highlighting the potential of SUSD2 as an immunotherapy target for cancer.

Mitochondrial calcium uniporter promotes phagocytosis-dependent activation of the NLRP3 inflammasome.

Mitochondria, a highly metabolically active organelle, have been shown to play an essential role in regulating innate immune function. Mitochondrial Ca2+ uptake via the mitochondrial Ca2+ uniporter (MCU) is an essential process regulating mitochondrial metabolism by targeting key enzymes involved in the tricarboxylic acid cycle (TCA). Accumulative evidence suggests MCU-dependent mitochondrial Ca2+ signaling may bridge the metabolic reprogramming and regulation of immune cell function. However, the mechanism by which MCU regulates inflammation and its related disease remains elusive. Here we report a critical role of MCU in promoting phagocytosis-dependent activation of NLRP3 (nucleotide-binding domain, leucine-rich repeat containing family, pyrin domain-containing 3) inflammasome by inhibiting phagolysosomal membrane repair. Myeloid deletion of MCU (McuΔmye) resulted in an attenuated phagolysosomal rupture, leading to decreased caspase-1 cleavage and interleukin (IL)-1ß release, in response to silica or alum challenge. In contrast, other inflammasome agonists such as adenosine triphosphate (ATP), nigericin, poly(dA:dT), and flagellin induced normal IL-1ß release in McuΔmye macrophages. Mechanistically, we demonstrated that decreased NLRP3 inflammasome activation in McuΔmye macrophages was caused by improved phagolysosomal membrane repair mediated by ESCRT (endosomal sorting complex required for transport)-III complex. Furthermore, McuΔmye mice showed a pronounced decrease in immune cell recruitment and IL-1ß production in alum-induced peritonitis, a typical IL-1-dependent inflammation model. In sum, our results identify a function of MCU in promoting phagocytosis-dependent NLRP3 inflammatory response via an ESCRT-mediated phagolysosomal membrane repair mechanism.

High-fat diet promotes liver tumorigenesis via palmitoylation and activation of AKT.

OBJECTIVE: Whether and how the PI3K-AKT pathway, a central node of metabolic homeostasis, is responsible for high-fat-induced non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) remain a mystery. Characterisation of AKT regulation in this setting will provide new strategies to combat HCC. DESIGN: Metabolite library screening disclosed that palmitic acid (PA) could activate AKT. In vivo and in vitro palmitoylation assay were employed to detect AKT palmitoylation. Diverse cell and mouse models, including generation of AKT1C77S and AKT1C224S knock-in cells, Zdhhc17 and Zdhhc24 knockout mice and Akt1C224S knock-in mice were employed. Human liver tissues from patients with NASH and HCC, hydrodynamic transfection mouse model, high-fat/high-cholesterol diet (HFHCD)-induced NASH/HCC mouse model and high-fat and methionine/choline-deficient diet (HFMCD)-induced NASH mouse model were also further explored for our mechanism studies. RESULTS: By screening a metabolite library, PA has been defined to activate AKT by promoting its palmitoyl modification, an essential step for growth factor-induced AKT activation. Biologically, a high-fat diet could promote AKT kinase activity, thereby promoting NASH and liver cancer. Mechanistically, palmitoyl binding anchors AKT to the cell membrane in a PIP3-independent manner, in part by preventing AKT from assembling into an inactive polymer. The palmitoyltransferases ZDHHC17/24 were characterised to palmitoylate AKT to exert oncogenic effects. Interestingly, the anti-obesity drug orlistat or specific penetrating peptides can effectively attenuate AKT palmitoylation and activation by restricting PA synthesis or repressing AKT modification, respectively, thereby antagonising liver tumorigenesis. CONCLUSIONS: Our findings elucidate a novel fine-tuned regulation of AKT by PA-ZDHHC17/24-mediated palmitoylation, and highlight tumour therapeutic strategies by taking PA-restricted diets, limiting PA synthesis, or directly targeting AKT palmitoylation.

Predicting the effects of mutations on protein solubility using graph convolution network and protein language model representation.

Solubility is one of the most important properties of protein. Protein solubility can be greatly changed by single amino acid mutations and the reduced protein solubility could lead to diseases. Since experimental methods to determine solubility are time-consuming and expensive, in-silico methods have been developed to predict the protein solubility changes caused by mutations mostly through protein evolution information. However, these methods are slow since it takes long time to obtain evolution information through multiple sequence alignment. In addition, these methods are of low performance because they do not fully utilize protein 3D structures due to a lack of experimental structures for most proteins. Here, we proposed a sequence-based method DeepMutSol to predict solubility change from residual mutations based on the Graph Convolutional Neural Network (GCN), where the protein graph was initiated according to predicted protein structure from Alphafold2, and the nodes (residues) were represented by protein language embeddings. To circumvent the small data of solubility changes, we further pretrained the model over absolute protein solubility. DeepMutSol was shown to outperform state-of-the-art methods in benchmark tests. In addition, we applied the method to clinically relevant genes from the ClinVar database and the predicted solubility changes were shown able to separate pathogenic mutations. All of the data sets and the source code are available at https://github.com/biomed-AI/DeepMutSol.

Forearm bone mineral density predicts screw loosening after lumbar fusion similar to lumbar Hounsfield unit value in patients with lumbar spondylolisthesis.

Preoperative bone density assessment is necessary to predict screw loosening. The forearm BMD is a useful predictor of BMD-related complications after lumbar operation. Our results show that the forearm BMD is as effective a predictor of screw loosening as the lumbar average HU value. Measurement of the forearm BMD may be a useful adjunct in predicting screw loosening following lumbar fusion. PURPOSE: To determine the relationship between forearm bone mineral density (BMD) and the risk of pedicle screw loosening in patients with lumbar spondylolisthesis. METHODS: We retrospectively evaluated 270 patients who underwent posterior lumbar interbody fusion for lumbar spondylolisthesis. The patients were divided into two groups on the basis of the with or without loose screws: the loosening group and the non-loosening group. The patient's gender, age, BMI, smoking and diabetes histories, and the operative segment were recorded as the basic information. The Hounsfield unit (HU) value for the BMD of the L1-4 lumbar was measured using computed tomography. The patient's distal one-third of the length of the radius and ulna of the non-dominant forearm was chosen as the site for dual-energy X-ray (DXA) bone density testing. RESULTS: The rate of screw loosening was 13% at a minimum 12 months follow-up. Average forearm BMD (0.461 ± 0.1 vs 0.577 ± 0.1, p < 0.001) and mean HU value (L1-4) (121.1 ± 27.3 vs 155.6 ± 32.2, p < 0.001) were lower in the screw loosening group than those in the non-loosening group. In multivariate logistic regression analysis, the forearm BMD (OR 0.840; 95%CI 0.797-0.886) and HU value (L1-4) (OR 0.952; 95%CI 0.935-0.969) were independent risk factor for screw loosening. The area under the curve (AUC) for the forearm BMD and HU value for prediction of pedicle screw loosening was 0.802 and 0.811. The forearm BMD cut-off for predicting pedicle screw loosening was 0.543 (sensitivity, 0.800; specificity, 0.864). CONCLUSIONS: The forearm BMD was an independent risk factor for loosening of the lumbar pedicle screws. The forearm BMD was a valid predictor of pedicle screw loosening in patients undergoing lumbar fusion, as was the CT HU value.

Silicon induces ROS scavengers, hormone signalling, antifungal metabolites, and silicon deposition against brown stripe disease in sugarcane.

Bipolaris setariae is known to cause brown stripe disease in sugarcane, resulting in significant yield losses. Silicon (Si) has the potential to enhance plant growth and biotic resistance. In this study, the impact of Si on brown stripe disease was investigated across susceptible and resistant sugarcane varieties, utilizing four Si concentrations (0, 15, 30, and 45 g per barrel of Na2SiO3·5H2O). Si significantly reduced the incidence of brown stripe disease (7.41-59.23%) and alleviated damage to sugarcane growth parameters, photosynthetic parameters, and photosynthetic pigments. Submicroscopic observations revealed that Si induced the accumulation of silicified cells in leaves, reduced spore accumulation, decreased stomatal size, and protected organelles from B. setariae damage. In addition, Si increased the activity of antioxidant enzymes (superoxide dismutase, peroxidase, and catalase), reduced reactive oxygen species production (malondialdehyde and hydrogen peroxide) and modulated the expression of genes associated with hormone signalling (PR1, TGA, AOS, AOC, LOX, PYL8, and SnRK2), leading to the accumulation of abscisic acid and jasmonic acid and inhibiting SA synthesis. Si also activated the activity of metabolism-related enzymes (polyphenol oxidase and phenylalanine ammonia lyase) and the gene expression of PAL-dependent genes (PAL, C4H, and 4CL), regulating the accumulation of metabolites, such as chlorogenic acid and lignin. The antifungal test showed that chlorogenic acid (15ug µL-1) had a significant inhibitory effect on the growth of B. setariae. This study is the first to demonstrate the inhibitory effect of Si on B. setariae in sugarcane, highlighting Si as a promising and environmentally friendly strategy for managing brown stripe disease.

Water quality drives the reconfiguration of riverine planktonic microbial food webs.

The food web is a cycle of matter and energy within river ecosystems. River environmental changes resulting from human activities are increasingly threatening the composition and diversity of global aquatic organisms and the multi-trophic networks. How multiple environmental factors influence food web patterns among multi-trophic microbial communities in rivers remains largely unknown. Using water quality evaluation and meta-omics techniques, we investigated the composition, structure and interaction characteristics, and drivers of food webs of microorganisms (archaea, bacteria, fungi, protists, metazoa, viridiplantae and viruses) at multiple trophic levels in different water quality environments (Classes II, III, and IV). First, water quality deterioration led to significant changes in the composition of the microbial community at multiple trophic levels, which were represented by the enrichment of Euryarchaeota in the archaeal community, the increase of r-strategists in the bacterial community, and the increase of the proportion of predators in the protist community. Second, deteriorating water quality resulted in a significant reduction in the dissimilarity of community structure (homogenization of community structure in Class III and IV waters). Of the symbiotic, parasitic, and predatory networks, the community networks in Class II water all showed the most stable symbiotic, parasitic, and predatory correlations (higher levels of modularity in the networks). In Class III and IV waters, nutrient inputs have led to increased reciprocal symbiosis and decreased competition between communities, which may have the risk of a positive feedback loop driving a system collapse. Finally, inputs of phosphorus and organic matter could be the main drivers of changes in the planktonic microbial food web in the Fen River. Overall, the results indicated the potential ecological risks of exogenous nutrient inputs, which were important for aquatic ecosystem conservation.

MYO1F regulates antifungal immunity by regulating acetylation of microtubules.

Opportunistic fungal infections have become one of the leading causes of death among immunocompromised patients, resulting in an estimated 1.5 million deaths each year worldwide. The molecular mechanisms that promote host defense against fungal infections remain elusive. Here, we find that Myosin IF (MYO1F), an unconventional myosin, promotes the expression of genes that are critical for antifungal innate immune signaling and proinflammatory responses. Mechanistically, MYO1F is required for dectin-induced α-tubulin acetylation, acting as an adaptor that recruits both the adaptor AP2A1 and α-tubulin N-acetyltransferase 1 to α-tubulin; in turn, these events control the membrane-to-cytoplasm trafficking of spleen tyrosine kinase and caspase recruitment domain-containing protein 9 Myo1f-deficient mice are more susceptible than their wild-type counterparts to the lethal sequelae of systemic infection with Candida albicans Notably, administration of Sirt2 deacetylase inhibitors, namely AGK2, AK-1, or AK-7, significantly increases the dectin-induced expression of proinflammatory genes in mouse bone marrow-derived macrophages and microglia, thereby protecting mice from both systemic and central nervous system C. albicans infections. AGK2 also promotes proinflammatory gene expression in human peripheral blood mononuclear cells after Dectin stimulation. Taken together, our findings describe a key role for MYO1F in promoting antifungal immunity by regulating the acetylation of α-tubulin and microtubules, and our findings suggest that Sirt2 deacetylase inhibitors may be developed as potential drugs for the treatment of fungal infections.

Toxicity factors to assess the ecological risk for soil microbial communities.

The toxicity factor (TF), a critical parameter within the potential ecological risk index (RI), is determined without accounting for microbial factors. It is considerable uncertainty exists concerning its validity for quantitatively assessing the influence of metal(loid)s on microorganisms. To evaluate the suitability of TF, we constructed microcosm experiments with varying RI levels (RI = 100, 200, 300, 500, and 700) by externally adding zinc (Zn), chromium (Cr), copper (Cu), lead (Pb), nickel (Ni), cadmium (Cd), and mercury (Hg) to uncontaminated soil (CK). Quantitative real-time PCR (qPCR) and high-throughput sequencing techniques were employed to measure the abundance and community of bacteria and fungi, and high-throughput qPCR was utilised to quantify functional genes associated with CNPS cycles. The results demonstrated that microbial diversity and function exhibited significant alterations (p < 0.05) in response to increasing RI levels, and the influences on microbial community structure, enzyme activity, and functional gene abundances were different due to the types of metal(loid)s treatments. At the same RI level, significant differences (p < 0.05) were discerned in microbial diversity and function across metal(loid) treatments, and these differences became more pronounced (p < 0.001) at higher levels. These findings suggest that TF may not be suitable for the quantitative assessment of microbial ecological risk. Therefore, we adjusted the TF by following three steps (1) determining the adjustment criteria, (2) deriving the initial TF, and (3) adjusting and optimizing the TF. Ultimately, the optimal adjusted TF was established as Zn = 1.5, Cr = 4.5, Cu = 6, Pb = 4.5, Ni = 5, Cd = 22, and Hg = 34. Our results provide a new reference for quantitatively assessing the ecological risks caused by metal(loid)s to microorganisms.

The PI3K-Akt-mTOR pathway mediates renal pericyte-myofibroblast transition by enhancing glycolysis through HKII.

BACKGROUND: Pericyte-myofibroblast transition (PMT) has been confirmed to contribute to renal fibrosis in several kidney diseases, and transforming growth factor-ß1 (TGF-ß1) is a well-known cytokine that drives PMT. However, the underlying mechanism has not been fully established, and little is known about the associated metabolic changes. METHODS: Bioinformatics analysis was used to identify transcriptomic changes during PMT. PDGFRß + pericytes were isolated using MACS, and an in vitro model of PMT was induced by 5 ng/ml TGF-ß1. Metabolites were analyzed by ultraperformance liquid chromatography (UPLC) and tandem mass spectrometry (MS). 2-Deoxyglucose (2-DG) was used to inhibit glycolysis via its actions on hexokinase (HK). The hexokinase II (HKII) plasmid was transfected into pericytes for HKII overexpression. LY294002 or rapamycin was used to inhibit the PI3K-Akt-mTOR pathway for mechanistic exploration. RESULTS: An increase in carbon metabolism during PMT was detected through bioinformatics and metabolomics analysis. We first detected increased levels of glycolysis and HKII expression in pericytes after stimulation with TGF-ß1 for 48 h, accompanied by increased expression of α-SMA, vimentin and desmin. Transdifferentiation was blunted when pericytes were pretreated with 2-DG, an inhibitor of glycolysis. The phosphorylation levels of PI3K, Akt and mTOR were elevated during PMT, and after inhibition of the PI3K-Akt-mTOR pathway with LY294002 or rapamycin, glycolysis in the TGF-ß1-treated pericytes was decreased. Moreover, PMT and HKII transcription and activity were blunted, but the plasmid-mediated overexpression of HKII rescued PMT inhibition. CONCLUSIONS: The expression and activity of HKII as well as the level of glycolysis were increased during PMT. Moreover, the PI3K-Akt-mTOR pathway regulates PMT by increasing glycolysis through HKII regulation.

Eco-friendly triboelectric nanogenerator based on degradable rape straw powder for monitoring human movement.

Green energy from the surrounding environment has great potential for reducing environmental pollution and sustainable development. Triboelectric nanogenerators (TENGs) are of great interest as they can easily harvest mechanical energy from the environment. Here, we present a triboelectric nanogenerator (RS-TENG) based on rape straw (RS), which was developed from a film composed of waste RS and polyvinyl alcohol (PVA). Due to the high content of carbonyl, hydroxyl and amino acid functional groups in RS, the ability of RS/PVA to lose electrons is increased. The proposed RS-TENG device with a size of 6.25 cm2exhibits open circuit voltage (78 V), short circuit current (5.3µA) performance under uniform external stress at a frequency of 3.5 Hz and 10 N in the cylinder motor. 104.5µW was obtained with a load resistance of 25 MΩ. Results obtained from degradability tests revealed that the RS/PVA film was able to degrade over a period of 30 d (In PBS solution). The RS-TENG produces a significantly high current signal under conditions of finger bending, elbow movements, and foot tapping. Practical tests of the RS-TENG have shown that it is a promising sensing device that will be widely used in the future.

Cutting Edge: EPHB2 Is a Coreceptor for Fungal Recognition and Phosphorylation of Syk in the Dectin-1 Signaling Pathway.

Invasive fungal infections have become a leading cause of death among immunocompromised patients, leading to around 1.5 million deaths per year globally. The molecular mechanisms by which hosts defend themselves against fungal infection remain largely unclear, which impedes the development of antifungal drugs and other treatment options. In this article, we show that the tyrosine kinase receptor EPH receptor B2 (EPHB2), together with dectin-1, recognizes ß-glucan and activates downstream signaling pathways. Mechanistically, we found that EPHB2 is a kinase for Syk and is required for Syk phosphorylation and activation after dectin-1 ligand stimulation, whereas dectin-1 is critical for the recruitment of Syk. Ephb2-deficient mice are susceptible to Candida albicans-induced fungemia model, which also supports the role of EPHB2 in antifungal immunity. Overall, we provide evidence that EPHB2 is a coreceptor for the recognition of dectin-1 ligands and plays an essential role in antifungal immunity by phosphorylating Syk.

Identification of a Long Noncoding RNA TRAF3IP2-AS1 as Key Regulator of IL-17 Signaling through the SRSF10-IRF1-Act1 Axis in Autoimmune Diseases.

IL-17A plays an essential role in the pathogenesis of many autoimmune diseases, including psoriasis and multiple sclerosis. Act1 is a critical adaptor in the IL-17A signaling pathway. In this study, we report that an anti-sense long noncoding RNA, TRAF3IP2-AS1, regulates Act1 expression and IL-17A signaling by recruiting SRSF10, which downregulates the expression of IRF1, a transcriptional factor of Act1. Interestingly, we found that a psoriasis-susceptible variant of TRAF3IP2-AS1 A4165G (rs13210247) is a gain-of-function mutant. Furthermore, we identified a mouse gene E130307A14-Rik that is homologous to TRAF3IP2-AS1 and has a similar ability to regulate Act1 expression and IL-17A signaling. Importantly, treatment with lentiviruses expressing E130307A14-Rik or SRSF10 yielded therapeutic effects in mouse models of psoriasis and experimental autoimmune encephalomyelitis. These findings suggest that TRAF3IP2-AS1 and/or SRSF10 may represent attractive therapeutic targets in the treatment of IL-17-related autoimmune diseases, such as psoriasis and multiple sclerosis.

Targeted VEGFA therapy in regulating early acute kidney injury and late fibrosis.

Damage to peritubular capillaries is a key process that contributes to acute kidney injury (AKI) progression. Vascular endothelial growth factor A (VEGFA) plays a critical role in maintaining the renal microvasculature. However, the physiological role of VEGFA in various AKI durations remains unclear. A severe unilateral ischemia‒reperfusion injury model was established to provide an overview of VEGFA expression and the peritubular microvascular density from acute to chronic injury in mouse kidneys. Therapeutic strategies involving early VEGFA supplementation protecting against acute injury and late anti-VEGFA treatment for fibrosis alleviation were analyzed. A proteomic analysis was conducted to determine the potential mechanism of renal fibrosis alleviation by anti-VEGFA. The results showed that two peaks of extraglomerular VEGFA expression were observed during AKI progression: one occurred at the early phase of AKI, and the other occurred during the transition to chronic kidney disease (CKD). Capillary rarefaction progressed despite the high expression of VEGFA at the CKD stage, and VEGFA was associated with interstitial fibrosis. Early VEGFA supplementation protected against renal injury by preserving microvessel structures and counteracting secondary tubular hypoxic insults, whereas late anti-VEGFA treatment attenuated renal fibrosis progression. The proteomic analysis highlighted an array of biological processes related to fibrosis alleviation by anti-VEGFA, which included regulation of supramolecular fiber organization, cell-matrix adhesion, fibroblast migration, and vasculogenesis. These findings establish the landscape of VEGFA expression and its dual roles during AKI progression, which provides the possibility for the orderly regulation of VEGFA to alleviate early acute injury and late fibrosis.

Kynurenine 3-Monooxygenase Gene SsCI51640 Is Required for Sporisorium scitamineum Mating/Filamentation by Regulating cAMP Pathway and Improving Sporidia Environmental Adaptability.

Sugarcane smut is a serious disease caused by Sporisorium scitamineum, which causes significant losses to the sugar industry. It is critical to reveal the molecular pathogenic mechanism of S. scitamineum to explore a new control strategy for sugarcane smut. On the basis of transcriptome sequencing data of two S. scitamineum strains with different pathogenicity, we identified the gene, SsCI51640, which was predicted to encode kynurenine 3-monooxygenase. In this study, we obtained knockout mutants and complementary mutants of this gene and identified gene function. The results showed that the sporidial growth rate and acid production ability of knockout mutants were significantly higher and stronger than those of the wild-type and complementary mutants. The growth of knockout mutants under abiotic stress (osmotic stress and cell wall stress) was significantly inhibited. In addition, the sexual mating ability and pathogenicity of knockout mutants were significantly reduced, while this phenomenon could be restored by adding exogenous cyclic adenosine monophosphate (cAMP). It is thus speculated that the SsCI51640 gene may regulate sexual mating and pathogenicity of S. scitamineum by the cAMP signaling pathway. Moreover, the SsCI51640 gene enhanced the sporidial environmental adaptability, which promoted sexual mating and development of pathogenicity. This study provides a theoretical basis for the molecular pathogenesis of S. scitamineum.

Comparative Biomechanical Analysis of Anterior Process Locking Plate Alone versus Combined with Percutaneous Cannulated Screw Fixation for Sanders Type II Calcaneal Fractures: A Finite Element Study.

BACKGROUND Calcaneal fractures are the most common tarsal bone fractures, and account for 75% of intra-articular fractures. The purpose of this study was to compare the biomechanical stability of the anterior process locking plate combined with the percutaneous cannulated screw fixation (screw group) versus the anterior process locking plate fixation alone (plate group) for the treatment of Sanders type II calcaneal fractures using finite element analysis to provide a theoretical basis for clinical work. MATERIAL AND METHODS We established a 3D model of Sanders type II calcaneal fracture; assigned material properties to the internal fixation systems; applied loads; set up analysis criteria; analyzed the displacement of the fracture, relative displacement, stress state of bone tissue, and internal fixation; and compared mechanical stability. RESULTS For Sanders type II A, II B, and II C calcaneal fractures, the degree of displacement and relative displacement of the fracture in the screw group was less than that of the plate group. For all subtypes of Sanders type II calcaneal fractures, the screw group had better mechanical stability than the plate group. CONCLUSIONS Both fixation methods (screw and plate group) were within a reasonable range for restoring the levelling effect of the joint surface and maintaining the strength of fixation, and both had good mechanical stability. Finite element analysis is a relatively reliable method, and biomechanics and clinical studies must further verify the experimental results.

Cigarettes smoking and e-cigarettes using among university students: a cross-section survey in Guangzhou, China, 2021.

BACKGROUND: There is an increase in the use of cigarettes and e-cigarettes worldwide, and the similar trends may be observed in young adults. Since 2014, e-cigarettes have become the most commonly used nicotine products among young adults (Sun et al., JAMA Netw Open 4:e2118788, 2021). With the increase in e-cigarette use and the decrease in use of cigarettes and other tobacco products, however, there is limited information about Chinese smokers, e-cigarettes users and trends in cigarettes and e-cigarettes use among university students. Therefore, our objective was to investigate the using status of cigarettes, e-cigarettes and smoking behavior among the students from 7 universities in Guangzhou, China. METHODS: Students at 7 different universities in Guangzhou were investigated online in 2021 through a cross-sectional survey. A total of 10,008 students were recruited and after screening, 9361 participants were adopted in our statistics. Descriptive analysis, Chi-square analysis, and multiple logistic regression analysis were used to explore the smoking status and influencing factors. RESULTS: The average age of the 9361 university students was 22.4 years (SD = 3.6). 58.3% of participants were male. 29.8% of the participants smoked or used e-cigarettes. Among the smokers and users of e-cigarettes, 16.7% were e-cigarettes only users, 35.0% were cigarettes only users, and 48.3% were dual users. Males were more likely to smoke or use e-cigarettes. Medical students, students from prestigious Chinese universities, and students with higher levels of education were less likely. Students with unhealthy lifestyles (e.g., drinking alcohol frequently, playing video games excessively, staying up late frequently) were more likely to smoke or use e-cigarettes. Emotion can have significant impacts on both cigarettes and e-cigarettes dual users when choosing cigarettes or e-cigarettes to use. More than half of dual users said they would choose cigarettes when they were depressed and e-cigarettes when they were happy. CONCLUSION: We identified factors influencing the use of cigarettes and e-cigarettes among university students in Guangzhou, China. Gender, education level background, specialization, lifestyle habits and emotion all influenced the use of cigarettes and e-cigarettes among university students in Guangzhou, China. Male, low education level, from non-prestigious Chinese universities or vocational schools, non-medical specialization, and presence of unhealthy lifestyles were influencing factors for the use of cigarettes and e-cigarettes among university students in Guangzhou and students with these factors were more likely to smoke or use e-cigarettes. Besides, emotions can influence dual users' choice of products. This study provides more information to better understand young people's preferences for cigarettes and e-cigarettes by elucidating the characteristics of cigarettes and e-cigarettes use, as well as related influencing factors, among university students in Guangzhou. Further research involving more variables connected to the use of cigarettes and e-cigarettes will be required in our future study.

Ultrasonic treatment alleviated cadmium stress in sugarcane via improving antioxidant activity and physiological and biochemical status.

Cadmium (Cd) is a toxic element that endangers crop growth and affects food safety and human health. Therefore, the study of Cd mitigation technology is important. Ultrasonic treatment can improve crop growth and enhance their ability to resist various abiotic stresses. In this study, the effect of ultrasonic treatment on alleviating sugarcane Cd stress was studied in a barrel experiment using sugarcane varieties 'ROC22' and 'LC05-136' as test materials. Sugarcane buds without ultrasonic treatment and with ultrasonic treatment (20-40 kHz mixed frequency ultrasound for 2 min, dry treatment) were planted in soil with Cd contents of 0, 50, 100, 250, and 500 mg·kg-1. Compared with non-ultrasonic treatment, Ultrasonic treatment significantly increased the activities of antioxidant enzymes in sugarcane, significantly increased the content of osmoregulation substances, significantly reduced the content of superoxide anion (the highest decreases reached 11.55%) and malondialdehyde (the highest decreases reached 20.59%), and significantly increased the expression level of metallothionein (MT)-related genes, with the expression of ScMT1 increased by 8.80-37.49% and the expression of ScMT2-1-5 increased by 1.55-69.33%. In addition, ultrasonic treatment significantly reduced the Cd contents in sugarcane roots, stems, leaves, bagasse, and juice (the highest reduction in Cd content was 49.18%). In general, ultrasonic treatment regulated the metabolism of reactive oxygen species and MT-related gene expression in sugarcane, increased the Cd tolerance of sugarcane, promoted photosynthesis in sugarcane leaves, improved root morphology, enhanced sugarcane growth, and increased cane and sugar yield.

Flexible Data Rate Allocation Using Non-Orthogonal Multiple Access (NOMA) in a Mode Division Multiplexing (MDM) Optical Power Splitter for System-on-Chip Networks.

We put forward and demonstrate a silicon photonics (SiPh)-based mode division multiplexed (MDM) optical power splitter that supports transverse-electric (TE) single-mode, dual-mode, and triple-mode (i.e., TE0, TE1, and TE2). An optical power splitter is needed for optical signal distribution and routing in optical interconnects. However, a traditional optical splitter only divides the power of the input optical signal. This means the same data information is received at all the output ports of the optical splitter. The powers at different output ports may change depending on the splitting ratio of the optical splitter. The main contributions of our proposed optical splitter are: (i) Different data information is received at different output ports of the optical splitter via the utilization of NOMA. By adjusting the power ratios of different channels in the digital domain (i.e., via software control) at the Tx, different channel data information can be received at different output ports of the splitter. It can increase the flexibility of optical signal distribution and routing. (ii) Besides, the proposed optical splitter can support the fundamental TE0 mode and the higher modes TE1, TE2, etc. Supporting mode-division multiplexing and multi-mode operation are important for future optical interconnects since the number of port counts is limited by the chip size. This can significantly increase the capacity besides wavelength division multiplexing (WDM) and spatial division multiplexing (SDM). The integrated SiPh MDM optical power splitter consists of a mode up-conversion section implemented by asymmetric directional couplers (ADCs) and a Y-branch structure for MDM power distribution. Here, we also propose and discuss the use of the Genetic algorithm (GA) for the MDM optical power splitter parameter optimization. Finally, to provide adjustable data rates at different output ports after the MDM optical power splitter, non-orthogonal multiple access-orthogonal frequency division multiplexing (NOMA-OFDM) is also employed. Experimental results validate that, in three modes (TE0, TE1, and TE2), user-1 and user-2 achieve data rates of (user-1: greater than 22 Gbit/s; user-2: greater than 12 Gbit/s) and (user-1: greater than 12 Gbit/s; user-2: 24 Gbit/s), respectively, at power-ratio (PR) = 2.0 or 3.0. Each channel meets the hard-decision forward-error-correction (HD-FEC, i.e., BER = 3.8 × 10-3) threshold. The proposed method allows flexible data rate allocation for multiple users for optical interconnects and system-on-chip networks.

Structure-aware protein-protein interaction site prediction using deep graph convolutional network.

MOTIVATION: Protein-protein interactions (PPI) play crucial roles in many biological processes, and identifying PPI sites is an important step for mechanistic understanding of diseases and design of novel drugs. Since experimental approaches for PPI site identification are expensive and time-consuming, many computational methods have been developed as screening tools. However, these methods are mostly based on neighbored features in sequence, and thus limited to capture spatial information. RESULTS: We propose a deep graph-based framework deep Graph convolutional network for Protein-Protein-Interacting Site prediction (GraphPPIS) for PPI site prediction, where the PPI site prediction problem was converted into a graph node classification task and solved by deep learning using the initial residual and identity mapping techniques. We showed that a deeper architecture (up to eight layers) allows significant performance improvement over other sequence-based and structure-based methods by more than 12.5% and 10.5% on AUPRC and MCC, respectively. Further analyses indicated that the predicted interacting sites by GraphPPIS are more spatially clustered and closer to the native ones even when false-positive predictions are made. The results highlight the importance of capturing spatially neighboring residues for interacting site prediction. AVAILABILITY AND IMPLEMENTATION: The datasets, the pre-computed features, and the source codes along with the pre-trained models of GraphPPIS are available at https://github.com/biomed-AI/GraphPPIS. The GraphPPIS web server is freely available at https://biomed.nscc-gz.cn/apps/GraphPPIS. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.