Charging CAR by electrostatic power.

Chimeric antigen receptor (CAR)-T cell therapy has emerged as a promising approach for cancer treatment. CAR is a synthetic immune receptor that recognizes tumor antigen and activates T cells through multiple signaling pathways. However, the current CAR design is not as robust as T cell receptor (TCR), a natural antigen receptor with high sensitivity and efficiency. TCR signaling relies on specific molecular interactions, and thus electrostatic force, the major force of molecular interactions, play critical roles. Understanding how electrostatic charge regulates TCR/CAR signaling events will facilitate the development of next-generation T cell therapies. This review summarizes recent findings on the roles of electrostatic interactions in both natural and synthetic immune receptor signaling, specifically that in CAR clustering and effector molecule recruitments, and highlights potential strategies for engineering CAR-T cell therapy by leveraging charge-based interactions.

FGF signaling promotes spreading of fat body precursors necessary for adult adipogenesis in Drosophila.

Knowledge of adipogenetic mechanisms is essential to understand and treat conditions affecting organismal metabolism and adipose tissue health. In Drosophila, mature adipose tissue (fat body) exists in larvae and adults. In contrast to the well-known development of the larval fat body from the embryonic mesoderm, adult adipogenesis has remained mysterious. Furthermore, conclusive proof of its physiological significance is lacking. Here, we show that the adult fat body originates from a pool of undifferentiated mesodermal precursors that migrate from the thorax into the abdomen during metamorphosis. Through in vivo imaging, we found that these precursors spread from the ventral midline and cover the inner surface of the abdomen in a process strikingly reminiscent of embryonic mesoderm migration, requiring fibroblast growth factor (FGF) signaling as well. FGF signaling guides migration dorsally and regulates adhesion to the substrate. After spreading is complete, precursor differentiation involves fat accumulation and cell fusion that produces mature binucleate and tetranucleate adipocytes. Finally, we show that flies where adult adipogenesis is impaired by knock down of FGF receptor Heartless or transcription factor Serpent display ectopic fat accumulation in oenocytes and decreased resistance to starvation. Our results reveal that adult adipogenesis occurs de novo during metamorphosis and demonstrate its crucial physiological role.

Identification of polymorphic markers for germplasm conservation of three precious Chinese palace goldfish using whole-genome sequencing.

China was the first country in the world to breed goldfish and has generated many unique goldfish varieties, including the most aristocratic Chinese palace goldfish. Due to the lack of scientific research on Chinese palace goldfish, their selection and breeding are mainly carried out through traditional hybridization, leading to serious inbreeding and the degradation of germplasm resources. To this end, whole-genome resequencing was performed to understand the genetic variation among three different varieties (eggpompons, goosehead, and tigerhead) from nine core conserved populations in China. A total of 15 polymorphic SSRs were developed for population genetics, and all tested populations were considered moderately polymorphic with an average polymorphism information content value of 0.4943. Genetic diversity in different varieties showed that all conserved populations were well protected with the potential for continued exploitation. This study provides reliable molecular tools and a basis for designing conservation and management programs in Chinese palace goldfish.

Effects of cadmium and zinc interactions on the physiological biochemistry and enrichment characteristics of Iris pseudacorus.

Compound pollution with cadmium (Cd) and zinc (Zn) is common in nature. The effects of compounded Cd and Zn on the growth and development of Iris pseudacorus in the environment and the plant's potential to remediate heavy metals in the environment remain unclear. In this study, the effects of single and combined Cd and Zn stress on I. pseudacorus growth and the enrichment of heavy metals in I. pseudacorus seedlings were investigated. The results showed that under Cd (160 µM) and Zn (800 µM) stress, plant growth was significantly inhibited and photosynthetic performance was affected. Cd+Zn200 (160 µM + 200 µM) reduced the levels of malondialdehyde, hydrogen peroxide, and non-protein thiols by 31.29%, 53.20%, and 13.29%, respectively, in the aboveground tissues compared with levels in the single Cd treatment. However, Cd+Zn800 (160 µM + 800 µM) had no effect. Cd and Zn800 inhibited the absorption of mineral elements, while Zn200 had little effect on plants. Compared with that for Cd treatment alone, Cd + Zn200 and Cd+Zn800 reduced the Cd content in aboveground tissues by 54.15% and 49.92%, respectively, but had no significant effect on Cd in the root system. Zn significantly reduced the Cd content in subcellular components and limited the content and proportion of Cd extracted using water and ethanol. These results suggest that a low supply of Zn reduces Cd accumulation in aboveground tissues by promoting antioxidant substances and heavy metal chelating agents, thus protecting the photosynthetic systems. The addition of Zn also reduced the mobility and bioavailability of Cd to alleviate its toxicity in I. pseudacorus.

The chromosome-level genome and key genes associated with mud-dwelling behavior and adaptations of hypoxia and noxious environments in loach (Misgurnus anguillicaudatus).

BACKGROUND: The loach (Misgurnus anguillicaudatus), the most widely distributed species of the family Cobitidae, displays a mud-dwelling behavior and intestinal air-breathing, inhabiting the muddy bottom of extensive freshwater habitats. However, lack of high-quality reference genome seriously limits the interpretation of the genetic basis of specialized adaptations of the loach to the adverse environments including but not limited to the extreme water temperature, hypoxic and noxious mud environment. RESULTS: This study generated a 1.10-Gb high-quality, chromosome-anchored genome assembly, with a contig N50 of 3.83 Mb. Multiple comparative genomic analyses found that proto-oncogene c-Fos (fos), a regulator of bone development, is positively selected in loach. Knockout of fos (ID: Mis0086400.1) led to severe osteopetrosis and movement difficulties, combined with the comparison results of bone mineral density, supporting the hypothesis that fos is associated with loach mud-dwelling behavior. Based on genomic and transcriptomic analysis, we identified two key elements involved in the intestinal air-breathing of loach: a novel gene (ID: mis0158000.1) and heat shock protein beta-1 (hspb1). The flavin-containing monooxygenase 5 (fmo5) genes, central to xenobiotic metabolism, undergone expansion in loach and were identified as differentially expressed genes in a drug stress trial. A fmo5-/- (ID: Mis0185930.1) loach displayed liver and intestine injury, indicating the importance of this gene to the adaptation of the loach to the noxious mud. CONCLUSIONS: Our work provides valuable insights into the genetic basis of biological adaptation to adverse environments.

Ecological impacts of the expansion of offshore wind farms on trophic level species of marine food chain.

The global demand for renewable energy has resulted in a rapid expansion of offshore wind farms (OWFs) and increased attention to the ecological impacts of OWFs on the marine ecosystem. Previous reviews mainly focused on the OWFs' impacts on individual species like birds, bats, or mammals. This review collected numerous field-measured data and simulated results to summarize the ecological impacts on phytoplankton, zooplankton, zoobenthos, fishes, and mammals from each trophic level and also analyze their interactions in the marine food chain. Phytoplankton and zooplankton are positively or adversely affected by the 'wave effect', 'shading effect', oxygen depletion and predation pressure, leading to a ± 10% fluctuation of primary production. Although zoobenthos are threatened transiently by habitat destruction with a reduction of around 60% in biomass in the construction stage, their abundance exhibited an over 90% increase, dominated by sessile species, due to the 'reef effect' in the operation stage. Marine fishes and mammals are to endure the interferences of noise and electromagnetic, but they are also aggregated around OWFs by the 'reef effect' and 'reserve effect'. Furthermore, the complexity of marine ecosystem would increase with a promotion of the total system biomass by 40% through trophic cascade effects strengthen and resource partitioning alternation triggered by the proliferation of filter-feeders. The suitable site selection, long-term monitoring, and life-cycle-assessment of ecological impacts of OWFs that are lacking in current literature have been described in this review, as well as the carbon emission and deposition.

Rank-in: enabling integrative analysis across microarray and RNA-seq for cancer.

Though transcriptomics technologies evolve rapidly in the past decades, integrative analysis of mixed data between microarray and RNA-seq remains challenging due to the inherent variability difference between them. Here, Rank-In was proposed to correct the nonbiological effects across the two technologies, enabling freely blended data for consolidated analysis. Rank-In was rigorously validated via the public cell and tissue samples tested by both technologies. On the two reference samples of the SEQC project, Rank-In not only perfectly classified the 44 profiles but also achieved the best accuracy of 0.9 on predicting TaqMan-validated DEGs. More importantly, on 327 Glioblastoma (GBM) profiles and 248, 523 heterogeneous colon cancer profiles respectively, only Rank-In can successfully discriminate every single cancer profile from normal controls, while the others cannot. Further on different sizes of mixed seq-array GBM profiles, Rank-In can robustly reproduce a median range of DEG overlapping from 0.74 to 0.83 among top genes, whereas the others never exceed 0.72. Being the first effective method enabling mixed data of cross-technology analysis, Rank-In welcomes hybrid of array and seq profiles for integrative study on large/small, paired/unpaired and balanced/imbalanced samples, opening possibility to reduce sampling space of clinical cancer patients. Rank-In can be accessed at http://www.badd-cao.net/rank-in/index.html.

Prevalence and risk factors for subjective cognitive decline and the correlation with objective cognition among community-dwelling older adults in China: Results from the Hubei memory and aging cohort study.

INTRODUCTION: The prevalence and risk factors for subjective cognitive decline (SCD) and its correlation with objective cognition decline (OCD) among community-dwelling older adults is inconsistent. METHODS: Older adults underwent neuropsychological and clinical evaluations to reach a consensus on diagnoses. RESULTS: This study included 7486 adults without mild cognitive impairment and dementia (mean age: 71.35 years [standard deviation = 5.40]). The sex-, age-, and residence-adjusted SCD prevalence was 58.33% overall (95% confidence interval: 58.29% to 58.37%), with higher rates of 61.25% and 59.87% in rural and female subgroups, respectively. SCD global and OCD language, SCD memory and OCD global, SCD and OCD memory, and SCD and OCD language were negatively correlated in fully adjusted models. Seven health and lifestyle factors were associated with an increased risk for SCD. DISCUSSION: SCD affected 58.33% of older adults and may indicate concurrent OCD, which should prompt the initiation of preventative intervention for dementia. HIGHLIGHTS: SCD affects 58.33% of older adults in China. SCD may indicate concurrent objective cognitive decline. Difficulty finding words and memory impairments may indicate a risk for AD. The presence of SCD may prompt preventative treatment initiation of MCI or dementia. Social network factors may be initial targets for the early prevention of SCD.

Exploring kinase family inhibitors and their moiety preferences using deep SHapley additive exPlanations.

BACKGROUND: While it has been known that human protein kinases mediate most signal transductions in cells and their dysfunction can result in inflammatory diseases and cancers, it remains a challenge to find effective kinase inhibitor as drugs for these diseases. One major challenge is the compensatory upregulation of related kinases following some critical kinase inhibition. To circumvent the compensatory effect, it is desirable to have inhibitors that inhibit all the kinases belonging to the same family, instead of targeting only a few kinases. However, finding inhibitors that target a whole kinase family is laborious and time consuming in wet lab. RESULTS: In this paper, we present a computational approach taking advantage of interpretable deep learning models to address this challenge. Specifically, we firstly collected 9,037 inhibitor bioassay results (with 3991 active and 5046 inactive pairs) for eight kinase families (including EGFR, Jak, GSK, CLK, PIM, PKD, Akt and PKG) from the ChEMBL25 Database and the Metz Kinase Profiling Data. We generated 238 binary moiety features for each inhibitor, and used the features as input to train eight deep neural networks (DNN) models to predict whether an inhibitor is active for each kinase family. We then employed the SHapley Additive exPlanations (SHAP) to analyze the importance of each moiety feature in each classification model, identifying moieties that are in the common kinase hinge sites across the eight kinase families, as well as moieties that are specific to some kinase families. We finally validated these identified moieties using experimental crystal structures to reveal their functional importance in kinase inhibition. CONCLUSION: With the SHAP methodology, we identified two common moieties for eight kinase families, 9 EGFR-specific moieties, and 6 Akt-specific moieties, that bear functional importance in kinase inhibition. Our result suggests that SHAP has the potential to help finding effective pan-kinase family inhibitors.

Identification of pan-kinase-family inhibitors using graph convolutional networks to reveal family-sensitive pre-moieties.

BACKGROUND: Human protein kinases, the key players in phosphoryl signal transduction, have been actively investigated as drug targets for complex diseases such as cancer, immune disorders, and Alzheimer's disease, with more than 60 successful drugs developed in the past 30 years. However, many of these single-kinase inhibitors show low efficacy and drug resistance has become an issue. Owing to the occurrence of highly conserved catalytic sites and shared signaling pathways within a kinase family, multi-target kinase inhibitors have attracted attention. RESULTS: To design and identify such pan-kinase family inhibitors (PKFIs), we proposed PKFI sets for eight families using 200,000 experimental bioactivity data points and applied a graph convolutional network (GCN) to build classification models. Furthermore, we identified and extracted family-sensitive (only present in a family) pre-moieties (parts of complete moieties) by utilizing a visualized explanation (i.e., where the model focuses on each input) method for deep learning, gradient-weighted class activation mapping (Grad-CAM). CONCLUSIONS: This study is the first to propose the PKFI sets, and our results point out and validate the power of GCN models in understanding the pre-moieties of PKFIs within and across different kinase families. Moreover, we highlight the discoverability of family-sensitive pre-moieties in PKFI identification and drug design.

Discovery of moiety preference by Shapley value in protein kinase family using random forest models.

BACKGROUND: Human protein kinases play important roles in cancers, are highly co-regulated by kinase families rather than a single kinase, and complementarily regulate signaling pathways. Even though there are > 100,000 protein kinase inhibitors, only 67 kinase drugs are currently approved by the Food and Drug Administration (FDA). RESULTS: In this study, we used "merged moiety-based interpretable features (MMIFs)," which merged four moiety-based compound features, including Checkmol fingerprint, PubChem fingerprint, rings in drugs, and in-house moieties as the input features for building random forest (RF) models. By using > 200,000 bioactivity test data, we classified inhibitors as kinase family inhibitors or non-inhibitors in the machine learning. The results showed that our RF models achieved good accuracy (> 0.8) for the 10 kinase families. In addition, we found kinase common and specific moieties across families using the Shapley Additive exPlanations (SHAP) approach. We also verified our results using protein kinase complex structures containing important interactions of the hinges, DFGs, or P-loops in the ATP pocket of active sites. CONCLUSIONS: In summary, we not only constructed highly accurate prediction models for predicting inhibitors of kinase families but also discovered common and specific inhibitor moieties between different kinase families, providing new opportunities for designing protein kinase inhibitors.

FRAGILE CULM 18 encodes a UDP-glucuronic acid decarboxylase required for xylan biosynthesis and plant growth in rice.

Although UDP-glucuronic acid decarboxylases (UXSs) have been well studied with regard to catalysing the conversion of UDP-glucuronic acid into UDP-xylose, their biological roles in grasses remain largely unknown. The rice (Oryza sativa) genome contains six UXSs, but none of them has been genetically characterized. Here, we reported on the characterization of a novel rice fragile culm mutant, fc18, which exhibited brittleness with altered cell wall and pleiotropic defects in growth. Map-based cloning and transgenic analyses revealed that the FC18 gene encodes a cytosol-localized OsUXS3 and is widely expressed with higher expression in xylan-rich tissues. Monosaccharide analysis showed that the xylose level was decreased in fc18, and cell wall fraction determinations confirmed that the xylan content in fc18 was lower, suggesting that UDP-xylose from FC18 participates in xylan biosynthesis. Moreover, the fc18 mutant displayed defective cellulose properties, which led to an enhancement in biomass saccharification. Furthermore, expression of genes involved in sugar metabolism and phytohormone signal transduction was largely altered in fc18. Consistent with this, the fc18 mutant exhibited significantly reduced free auxin (indole-3-acetic acid) content and lower expression levels of PIN family genes compared with wild type. Our work reveals the physiological roles of FC18/UXS3 in xylan biosynthesis, cellulose deposition, and plant growth in rice.

Iron-Activated Carbon Systems to Enhance Aboriginal Aerobic Denitrifying Bacterial Consortium for Improved Treatment of Micro-Polluted Reservoir Water: Performances, Mechanisms, and Implications.

Although many source waterbodies face nitrogen pollution problems, the lack of organic electron donors causes difficulties when aerobic denitrifying bacteria are used to treat micro-polluted water. Different forms of iron with granular activated carbon (AC) as carriers were used to stimulate aboriginal microorganisms for the purification of micro-polluted source water. Compared with the iron-absent AC system, targeted pollutants were significantly removed (75.76% for nitrate nitrogen, 95.90% for total phosphorus, and 80.59% for chemical oxygen demand) in the sponge-iron-modified AC system, which indicated that iron promoted the physical and chemical removal of pollutants. In addition, high-throughput sequencing showed that bacterial distribution and interaction were changed by ion dosage, which was beneficial for pollutant transformation and reduction. Microbial functions, such as pollutant removal and expression of functional enzymes that were responsible for the transformation of nitrate nitrogen to ammonia, were highly efficient in iron-applied systems. This study provides an innovative strategy to strengthen in situ remediation of micro-pollution in waterbodies.

Co-overexpression of TRAIL and Smac sensitizes MDA-MB-231 cells to radiation through apoptosis depending on mitochondrial pathway.

Pro-apoptosis in cancer cells has been proposed as a beneficial therapeutic strategy for potentiating the anticancer effects of radiotherapy. TNF-related apoptosis inducing ligand (TRAIL) and Second mitochondria derived activator of caspase (Smac) can induce cell apoptosis. Herein, we designed a conditionally replicating adenoviral co-overexpression vector of TRAIL and Smac regulated by the Egr1 promoter, in which hTERT, E1A-E1B and E1B55K genes were inserted to achieve enhanced tumor targeting characteristics. After breast cancer MDA-MB-231 cells were infected and irradiated, cellular proliferation and colony formation were measured, apoptotic rate was detected by FCM after AnnexinV-FITC/PI staining. To explore the molecular mechanisms of apoptosis, mRNA and protein levels of TRAIL, Smac, Cytochrome c (Cyt c), death receptor 5 (DR5), caspase-8, -9 and -3 were measured by quantitative real-time PCR, ELISA and Western blot, and caspase-3 activity was detected using caspase-3 activity kits. The results showed that TRAIL and/or Smac overexpression enhanced proliferation inhibition and radio-sensitivity through apoptosis. In addition, the combination of IR and overexpression of TRAIL and/or Smac can activate more apoptosis in tumor cells, and the transcriptional levels and protein expressions of Cyt c, DR5, caspase-8, -9 and -3 had similar regularity with apoptotic changes, indicating the molecular mechanisms of TRAIL and Smac involves the mitochondrial pathway. Our findings may have implications for novel radiotherapy plans for breast tumor treatment.

Expression profiles of cdca9 related to ovarian development in loach (Misgurnus anguillicaudatus).

The function of borealin proteins has been widely reported in the cell division of animals. Nonetheless, there is little research about their only known paralogue (cell division cycle associated 9, cdca9). In this study, cdca9 was investigated in loach (Misgurnus anguillicaudatus) for the first time. cdca9 was highly expressed in the embryo before the gastrula stage, and it was predominantly expressed in the ovary, especially in the oocytes of stage II. In conclusion, this study reveals a potential function of cdca9 in the early embryogenesis and ovarian development of fish.

CirPred, the first structure modeling and linker design system for circularly permuted proteins.

BACKGROUND: This work aims to help develop new protein engineering techniques based on a structural rearrangement phenomenon called circular permutation (CP), equivalent to connecting the native termini of a protein followed by creating new termini at another site. Although CP has been applied in many fields, its implementation is still costly because of inevitable trials and errors. RESULTS: Here we present CirPred, a structure modeling and termini linker design method for circularly permuted proteins. Compared with state-of-the-art protein structure modeling methods, CirPred is the only one fully capable of both circularly-permuted modeling and traditional co-linear modeling. CirPred performs well when the permutant shares low sequence identity with the native protein and even when the permutant adopts a different conformation from the native protein because of three-dimensional (3D) domain swapping. Linker redesign experiments demonstrated that the linker design algorithm of CirPred achieved subangstrom accuracy. CONCLUSIONS: The CirPred system is capable of (1) predicting the structure of circular permutants, (2) designing termini linkers, (3) performing traditional co-linear protein structure modeling, and (4) identifying the CP-induced occurrence of 3D domain swapping. This method is supposed helpful for broadening the application of CP, and its web server is available at http://10.life.nctu.edu.tw/CirPred/ and http://lo.life.nctu.edu.tw/CirPred/ .

Polarization insensitive, metamaterial absorber-enhanced long-wave infrared detector.

Detecting low energy photons, such as photons in the long-wave infrared range, is a technically challenging proposition using naturally occurring materials. In order to address this challenge, we herein demonstrate a micro-bolometer featuring an integrated metamaterial absorber (MA), which takes advantage of the resonant absorption and frequency selective properties of the MA. Importantly, our micro-bolometer exhibits polarization insensitivity and high absorption due to a novel metal-insulator-metal (MIM) absorber design, operating at 8-12 µm wavelength. The metamaterial structures we report herein feature an interconnected design, optimized towards their application to micro-bolometer-based, long-wave infrared detection. The micro-bolometers were fabricated using a combination of conventional photolithography and electron beam lithography (EBL), the latter owing to the small feature sizes within the design. The absorption response was designed using the coupled mode theory (CMT) and the finite integration technique, with the fabricated devices characterized using Fourier-transform infrared spectroscopy (FTIR). The metamaterial-based micro-bolometer exhibits a responsivity of approximately 198 V/W over the 8-12 µm wavelength regime, detectivity of ∼ 0.6 × 109 Jones, thermal response time of ∼ 3.3 ms, and a noise equivalent temperature difference (NETD) of ∼33 mK under 1mA biasing current at room-temperature and atmosphere pressure. The ultimate detectivity and NETD are limited by Johnson noise and heat loss with thermal convection through air; however, further optimization could be achieved by reducing the thermal conductivity via vacuum packaging. Under vacuum conditions, the detectivity may be increased in excess of two-fold, to ∼ 1.5 × 109 Jones. Finally, an infrared image of a soldering iron was generated using a single-pixel imaging process, serving as proof-of-concept of this detection platform. The results presented in this work pave the road towards high-efficiency and frequency-selective detection in the long-wave infrared range through the integration of infrared MAs with micro-bolometers.

Distal Electroacupuncture at the LI4 Acupoint Reduces CFA-Induced Inflammatory Pain via the Brain TRPV1 Signaling Pathway.

There is accumulating evidence supporting electroacupuncture's (EA) therapeutic effects. In mice, local EA reliably attenuates inflammatory pain and increases the transient receptor potential cation channel, subfamily V, member 1 (TRPV1). However, the effect of distal acupoint EA on pain control has rarely been studied. We used a mouse model to investigate the analgesic effect of distal EA by measuring TRPV1 expression in the brain. Complete Freund's adjuvant (CFA) was injected into mice's hind paws to induce inflammatory pain. The EA-treated group received EA at the LI4 acupoint on the bilateral forefeet on the second and the third days, whereas the control group underwent sham manipulation. Mechanical and thermal pain behavior tests showed that the EA-treated group experienced inflammatory pain alleviation immediately after EA, which did not occur in the sham group. Additionally, following CFA injection, the expression of TRPV1-associated molecules such as phosphorylated protein kinase A (pPKA), extracelluar signal-regulated kinase (pERK), and cAMP-response-element-binding protein (pCREB) increased in the prefrontal cortex (PFC) and the hypothalamus but decreased in the periaqueductal gray (PAG) area. These changes were significantly attenuated by EA but not sham EA. Our results show an analgesic effect of distal EA, which is based on the traditional Chinese medicine theory. The mechanism underlying this analgesic effect involves TRPV1 in the PFC, the hypothalamus, and the PAG. These novel findings are relevant for the evaluation and the treatment of clinical inflammatory pain syndrome.

Corylin inhibits LPS-induced inflammatory response and attenuates the activation of NLRP3 inflammasome in microglia.

BACKGROUND: Inflammation has been found to be associated with many neurodegenerative diseases, including Parkinson's and dementia. Attenuation of microglia-induced inflammation is a strategy that impedes the progression of neurodegenerative diseases. METHODS: We used lipopolysaccharide (LPS) to simulate murine microglia cells (BV2 cells) as an experimental model to mimic the inflammatory environment in the brain. In addition, we examined the anti-inflammatory ability of corylin, a main compound isolated from Psoralea corylifolia L. that is commonly used in Chinese herbal medicine. The production of nitric oxide (NO) by LPS-activated BV2 cells was measured using Griess reaction. The secretion of proinflammatory cytokines including tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) by LPS-activated BV2 cells was analyzed using enzyme-linked immunosorbent assay (ELISA). The expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase-activation and recruitment domain (ASC), caspase-1, IL-1ß and mitogen-activated protein kinases (MAPKs) in LPS-activated BV2 cells was examined by Western blot. RESULTS: Our experimental results demonstrated that corylin suppressed the production of NO and proinflammatory cytokines by LPS-activated BV2 cells. In addition, corylin inhibited the expression of iNOS and COX-2, attenuated the phosphorylation of ERK, JNK and p38, decreased the expression of NLRP3 and ASC, and repressed the activation of caspase-1 and IL-1ß by LPS-activated BV2 cells. CONCLUSION: Our results indicate the anti-inflammatory effects of corylin acted through attenuating LPS-induced inflammation and inhibiting the activation of NLRP3 inflammasome in LPS-activated BV2 cells. These results suggest that corylin might have potential in treating brain inflammation and attenuating the progression of neurodegeneration diseases.

Genetic enhancement of lodging resistance in rice due to the key cell wall polymer lignin, which affects stem characteristics.

Lodging in crops seriously restricts plant growth and grain production. The genetic modification of cell walls to enhance plant mechanical strength has been suggested as a promising approach toward improving lodging resistance. However, because of the complexity of the plant cell wall, the exact effects of its polymers on plant lodging resistance remain elusive. To address this issue, we performed large-scale analyses of a total of 56 rice (Oryza sativa L.) varieties that displayed distinct cell wall component and lodging index. Lignin was identified as the key cell wall polymer that positively determines lodging resistance in rice. Correlation analysis between cell wall composition and plant morphological characteristics revealed that lignin enhanced rice lodging resistance by largely increasing the mechanical strength of the basal stem and reducing plant height. Further characterization of four representative rice varieties, ShenNong9903, YanJian218, KongYu131, and ShenNongK33, displaying varied levels of lodging resistance, revealed the multiple candidate genes (PAL, CoMT, 4CL3, CAD2, CAD7 and CCR20) responsible for increasing lignin level. Hence, our results demonstrate that the high lignin level in the cell wall predominately improves lodging resistance and suggest target genes for the genetic modification of lignin towards breeding rice with high lodging resistance.