TCR-induced sumoylation of the kinase PKC-θ controls T cell synapse organization and T cell activation.

Sumoylation regulates many cellular processes, but its role in signaling via the T cell antigen receptor (TCR) remains unknown. We found that the kinase PKC-θ was sumoylated upon costimulation with antigen or via the TCR plus the coreceptor CD28, with Lys325 and Lys506 being the main sumoylation sites. We identified the SUMO E3 ligase PIASxß as a ligase for PKC-θ. Analysis of primary mouse and human T cells revealed that sumoylation of PKC-θ was essential for T cell activation. Desumoylation did not affect the catalytic activity of PKC-θ but inhibited the association of CD28 with PKC-θ and filamin A and impaired the assembly of a mature immunological synapse and central co-accumulation of PKC-θ and CD28. Our findings demonstrate that sumoylation controls TCR-proximal signaling and that sumoylation of PKC-θ is essential for the formation of a mature immunological synapse and T cell activation.

Identification of a novel amphioxus leucine-rich repeat receptor involved in phagocytosis reveals a role for Slit2-N-type LRR in bacterial elimination.

The basal chordate amphioxus is a model for tracing the origin and evolution of vertebrate immunity. To explore the evolution of immunoreceptor signaling pathways, we searched the associated receptors of the amphioxus Branchiostoma belcheri (Bb) homolog of immunoreceptor signaling adaptor protein Grb2. Mass-spectrum analysis of BbGrb2 immunoprecipitates from B. belcheri intestine lysates revealed a folate receptor (FR) domain- and leucine-rich repeat (LRR)-containing protein (FrLRR). Sequence and structural analysis showed that FrLRR is a membrane protein with a predicted curved solenoid structure. The N-terminal Fr domain contains very few folate-binding sites; the following LRR region is a Slit2-type LRR, and a GPI-anchored site was predicted at the C-terminus. RT-PCR analysis showed FrLRR is a transcription-mediated fusion gene of BbFR-like and BbSlit2-N-like genes. Genomic DNA structure analysis implied the B. belcheri FrLRR gene locus and the corresponding locus in Branchiostoma floridae might be generated by exon shuffling of a Slit2-N-like gene into an FR gene. RT-qPCR, immunostaining, and immunoblot results showed that FrLRR was primarily distributed in B. belcheri intestinal tissue. We further demonstrated that FrLRR localized to the cell membrane and lysosomes. Functionally, FrLRR mediated and promoted bacteria-binding and phagocytosis, and FrLRR antibody blocking or Grb2 knockdown inhibited FrLRR-mediated phagocytosis. Interestingly, we found that human Slit2-N (hSlit2-N) also mediated direct bacteria-binding and phagocytosis which was inhibited by Slit2-N antibody blocking or Grb2 knockdown. Together, these results indicate FrLRR and hSlit2-N may function as phagocytotic-receptors to promote phagocytosis through Grb2, implying the Slit2-N-type-LRR-containing proteins play a role in bacterial binding and elimination.

Adaptive Multiple Comparison Sequential Design (AMCSD) for clinical trials.

We propose an adaptive sequential testing procedure for clinical trials that test the efficacy of multiple treatment options, such as dose/regimen, different drugs, sub-populations, endpoints, or a mixture of them in one trial. At any interim analyses, sample size re-estimation can be conducted, and any option can be dropped for lack of efficacy or unsatisfactory safety profile. Inference after the trial, including p-value, conservative point estimate and confidence intervals, are provided.

Adaptive two-stage seamless sequential design for clinical trials.

We propose an adaptive sequential testing procedure for the selection and testing of multiple treatment options, such as dose/regimen, different drugs, sub-populations, endpoints, or a mixture of them in a seamlessly combined phase II/III trial. The selection is to be made at the end of phase 2 stage. Unlike in many of the published literature, the selection rule is not required to be to "select the best", and does not need to be pre-specified, which provides flexibility and allows the trial investigators to use any efficacy and safety information/criteria, or surrogate or intermediate endpoint to make the selection. Sample size and power calculations are provided. The calculations have been confirmed to be accurate by simulations. Interim analysis can be performed after the selection, sample size can be modified if the observed efficacy deviates from the assumed. Inference after the trial, including p-value, median unbiased point estimate and confidence intervals, are provided. By applying a dominance theorem, the procedure can be applied to normal, binary, Poisson, negative binomial distributed endpoints and time-to-event endpoints, and a mixture of these distributions (in trials involving endpoint selection).

The score-goldilocks design for phase 3 clinical trials.

In this paper, we propose a new Bayesian adaptive design, score-goldilocks design, which has the same algorithmic idea as goldilocks design. The score-goldilocks design leads to a uniform formula for calculating the probability of trial success for different endpoint trials by using the normal approximation. The simulation results show that the score-goldilocks design is not only very similar to the goldilocks design in terms of operating characteristics such as type 1 error, power, average sample size, probability of stop for futility, and probability of early stop for success, but also greatly saves the calculation time and improves the operation efficiency.

Alterations and associations between lung microbiota and metabolite profiles in silica-induced lung injury.

Silicosis, caused by silica exposure, is the most widespread and deadliest occupational disease. However, effective treatments are lacking. Therefore, it is crucial to elucidate the mechanisms and targets involved in the development of silicosis. We investigated the basic processes of silicosis development and onset at different exposure durations (2 or 4 weeks) using various techniques such as histopathology, immunohistochemistry, Enzyme linked immunosorbent assay(ELISA),16 S rRNA, and untargeted metabolomics.These results indicate that exposure to silica leads to progressive damage to lung tissue with significant deterioration observed over time. Time-dependent cytokines such as the IL-4, IL-13, and IL-6 are detected in lung lavage fluid, the model group consistently exhibited elevated levels of these cytokines, indicating a persistent and worsening inflammatory response in the lungs. Meanwhile, HE and Masson results show that 4-week exposure to silica causes more obvious lung injury and pulmonary fibrosis. Besides, the model group consistently exhibited a distinct lung bacterial population, known as the Lachnospiraceae_NK4A136_group, regardless of exposure duration. However, with increasing exposure duration, specific temporal changes were observed in lung bacterial populations, including Haliangium, Allobaculum, and Sandaracinus (at 4 weeks; p < 0.05). Furthermore, our study revealed a strong correlation between the mechanism of silica-induced lung injury and three factors: oxidative stress, impaired lipid metabolism, and imbalanced amino acid metabolism. We observed a close correlation between cytokine levels, changes in lung microbiota, and metabolic disturbances during various exposure periods. These findings propose that a possible mechanism of silica-induced lung injury involves the interplay of cytokines, lung microbiota, and metabolites.

The use of amino acids and their derivates to mitigate against pesticide-induced toxicity.

Exposure to pesticides induces oxidative stress and deleterious effects on various tissues in non-target organisms. Numerous models investigating pesticide exposure have demonstrated metabolic disturbances such as imbalances in amino acid levels within the organism. One potentially effective strategy to mitigate pesticide toxicity involves dietary intervention by supplementing exogenous amino acids and their derivates to augment the body's antioxidant capacity and mitigate pesticide-induced oxidative harm, whose mechanism including bolstering glutathione synthesis, regulating arginine-NO metabolism, mitochondria-related oxidative stress, and the open of ion channels, as well as enhancing intestinal microecology. Enhancing glutathione synthesis through supplementation of substrates N-acetylcysteine and glycine is regarded as a potent mechanism to achieve this. Selection of appropriate amino acids or their derivates for supplementation, and determining an appropriate dosage, are of the utmost importance for effective mitigation of pesticide-induced oxidative harm. More experimentation is required that involves large population samples to validate the efficacy of dietary intervention strategies, as well as to determine the effects of amino acids and their derivates on long-term and low-dose pesticide exposure. This review provides insights to guide future research aimed at preventing and alleviating pesticide toxicity through dietary intervention of amino acids and their derivates.

Structure, physicochemical properties, and biological activities of protein hydrolysates from Zanthoxylum seed.

BACKGROUND: Zanthoxylum seed, as a low-cost and easily accessible plant protein resource, has good potential in the food industry. But protein and its hydrolysates from Zanthoxylum seed are underutilized due to the dearth of studies on them. This study aimed to investigate the structure and physicochemical and biological activities of Zanthoxylum seed protein (ZSP) hydrolysates prepared using Protamex®, Alcalase®, Neutrase®, trypsin, or pepsin. RESULTS: Hydrolysis using each of the five enzymes diminished average particle size and molecular weight of ZSP but increased random coil content. ZSP hydrolysate prepared using pepsin had the highest degree of hydrolysis (24.07%) and the smallest molecular weight (<13 kDa) and average particle size (129.80 nm) with the highest solubility (98.9%). In contrast, ZSP hydrolysate prepared using Alcalase had the highest surface hydrophobicity and foaming capacity (88.89%), as well as the lowest foam stability (45.00%). Moreover, ZSP hydrolysate prepared using Alcalase exhibited the best hydroxyl-radical scavenging (half maximal inhibitory concentration (IC50 ) 1.94 mg mL-1 ) and ferrous-ion chelating (IC50 0.61 mg mL-1 ) activities. Additionally, ZSP hydrolysate prepared using pepsin displayed the highest angiotensin-converting enzyme inhibition activity (IC50 0.54 mg mL-1 ). CONCLUSION: These data showed that enzyme hydrolysis improved the physicochemical properties of ZSP, and enzymatic hydrolysates of ZSP exhibited significant biological activity. These results provided validation for application of ZSP enzymatic hydrolysates as antioxidants and antihypertensive agents in the food or medicinal industries. © 2023 Society of Chemical Industry.

Structure, functional and physicochemical properties of lotus seed protein under different pH environments.

BACKGROUND: The present study investigated the structure, functional and physicochemical properties of lotus seed protein (LSP) under different pH environments. The structures of LSP were characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Fourier transform infrared spectroscopy (FTIR), zeta potential, particle size distributions, free sulfhydryl and rheological properties. The functional and physicochemical properties of LSP were characterized by color, foaming property, emulsification property, solubility, oil holding capacity, water holding capacity, differential scanning calorimetry analysis and surface hydrophobicity. RESULTS: LSP was mainly composed of eight subunits (18, 25, 31, 47, 51, 56, 65 and 151 kDa), in which the richest band was 25 kDa. FTIR results showed that LSP had high total contents of α-helix and ß-sheet (44.81-46.85%) in acidic environments. Meanwhile, there was more ß-structure and random structure in neutral and alkaline environments (pH 7.0 and 9.0). At pH 5.0, LSP had large particle size (1576.98 nm), high emulsion stability index (91.43 min), foaming stability (75.69%) and water holding capacity (2.21 g g-1), but low solubility (35.98%), free sulfhydryl content (1.95 µmol g-1) and surface hydrophobicity (780). DSC analysis showed the denaturation temperatures (82.23 °C) of LSP at pH 5.0 was higher than those (80.10, 80.52 and 71.82 °C) at pH 3.0, 7.0 and 9.0. The analysis of rheological properties showed that LSP gel had high stability and great strength in an alkaline environment. CONCLUSION: The findings of the present study are anticipated to serve as a valuable reference for the implementation of LSP in the food industry. © 2024 Society of Chemical Industry.

The structural characteristics and physicochemical properties of mung bean protein hydrolysate of protamex induced by ultrasound.

BACKGROUND: The limited physicochemical properties (such as low foaming and emulsifying capacity) of mung bean protein hydrolysate restrict its application in the food industry. Ultrasound treatment could change the structures of protein hydrolysate to accordingly affect its physicochemical properties. The aim of this study was to investigate the effects of ultrasound treatment on the structural and physicochemical properties of mung bean protein hydrolysate of protamex (MBHP). The structural characteristics of MBHP were evaluated using tricine sodium dodecylsulfate-polyacrylamide gel electrophoresis, laser scattering, fluorescence spectrometry, etc. Solubility, fat absorption capacity and foaming, emulsifying and thermal properties were determined to characterize the physicochemical properties of MBHP. RESULTS: MBHP and ultrasonicated-MBHPs (UT-MBHPs) all contained five main bands of 25.8, 12.1, 5.6, 4.8 and 3.9 kDa, illustrating that ultrasound did not change the subunits of MBHP. Ultrasound treatment increased the contents of α-helix, ß-sheet and random coil and enhanced the intrinsic fluorescence intensity of MBHP, but decreased the content of ß-turn, which demonstrated that ultrasound modified the secondary and tertiary structures of MBHP. UT-MBHPs exhibited higher solubility, foaming capacity and emulsifying properties than MBHP, among which MBHP-330 W had the highest solubility (97.32%), foaming capacity (200%), emulsification activity index (306.96 m2 g-1 ) and emulsion stability index (94.80%) at pH 9.0. CONCLUSION: Ultrasound treatment enhanced the physicochemical properties of MBHP, which could broaden its application as a vital ingredient in the food industry. © 2023 Society of Chemical Industry.

Icariin-Curcumol promotes docetaxel sensitivity in prostate cancer through modulation of the PI3K-Akt signaling pathway and the Warburg effect.

BACKGROUND: Docetaxel (DTX) resistance reduces therapeutic efficacy in prostate cancer (PCa). Accumulating reports support the role of phytochemicals in the reversal of DTX resistance. This study aimed to determine whether Epimedium brevicornu and Curcuma zedoaria extracts (ECe), specially icariin-curcumol, attenuates DTX resistance and explore their potential mechanisms. METHODS: Regulatory pathways were predicted between ECe active ingredients and PCa using network pharmacology. DTX-resistant cell LNCaP/R were established based on DTX-sensitive LNCaP, and xenograft models were further established. Active ingredients in ECe by HLPC-MS were identified. The binding of icariin and curcumol to the target was analyzed by molecular docking. Biochemical experiments were applied to determine the possible mechanisms by which Icariin-Curcumol regulates DTX sensitivity. RESULTS: Akt1 and the PI3K-Akt signaling pathway were predicted as the primary functional target between drug and PCa. ECe and DTX inhibited xenograft tumor growth, inflammation, cell viability and promoted apoptosis. Icariin and curcumol were detected in ECe, and icariin and curcumol docked with Akt1. ECe, Icariin-Curcumol and DTX downregulated AR, PSA, PI3K, Akt1, mTOR, and HIF-1ɑ. Moreover, ECe, Icariin-Curcumol and DTX increased glucose and PDH, decreased lactic acid, ATP and LDH, and downregulated c-Myc, hnRNPs, VEGF, PFK1, and PKM2. Notably, the anti-PCa effect of DTX was attenuated compared to ECe or Icariin-Curcumol in the LNCaP/R model. The combined effect of Icariin-Curcumol and DTX was superior to that of DTX. CONCLUSION: Our data support that Icariin-Curcumol reverses DTX resistance by inhibiting the PI3K-Akt signaling and the Warburg effect, providing new ideas for improving therapeutic measures for PCa.

RNAi assays in the striped flea beetle (Phyllotreta striolata) suggest Psγ-COPI and PsArf1COPI as potential molecular targets for pest control.

Phyllotreta striolata (Fabricius), commonly known as the striped flea beetle (SFB), is a notorious insect pest that attacks Brassicaceae plants worldwide, leading to tremendous economic losses. RNA interference (RNAi) has been proposed as a promising strategy for sustainable and eco-friendly pest control. In this study, a total of nine housekeeping genes including PsVATPA, PsHSP90, PsEF1A, PsRPL6, PsRPS24, PsActin, PsTUBA, PsRPS18, and PsRPL4 were evaluated under four different conditions (organization, population, sex, and RNAi). PsEF1A and PsVATPA were identified as the best reference genes for RNAi bioassay. Furthermore, a total of 24 target genes were selected to investigate their RNAi effects in SFB adults with double-stranded RNAs (dsRNAs), five of them showed significant mortality (28.00% to 70.00%), namely Psα-COPI, Psß-COPI, PsRPS18, Psγ-COPI, and PsArf1COPI. We found that gene transcript levels of the two most lethal genes, Psγ-COPI and PsArf1COPI, were significantly decreased after treated with the target dsRNAs either by feeding or injection method. The findings from this study demonstrated that the introduction of dsRNAs via oral feedings or injection induces the RNAi-mediated silencing of target genes and can lead to insect mortality. Overall, the identified target genes can be explored in developing RNAi-based insecticides for SFB control.

Changes in quality components and antioxidant activity of peony seed soy sauce during low-salt solid-state fermentation.

BACKGROUND: In this study, the fermentation conditions of peony seed soy sauce (PSSS) koji were optimized by response surface method, and the quality components and antioxidant activity of PSSS were investigated at different low-salt solid-state fermentation stages. RESULTS: Results of response surface method showed that the optimal fermentation conditions were 460.6 g kg-1 water content, 48.6 h culture time, 31.5 °C culture temperature and ratio 2.1:1 (w/w) of peony seed meal:wheat bran, with the highest neutral protease activity (2193.78 U g-1 ) of PSSS koji. PSSS had the highest amino acid nitrogen (7.69 g L-1 ), salt-free soluble solids (185.26 g L-1 ), total free amino acids (49.03 g L-1 ), essential free amino acids (19.58 g L-1 ) and umami free amino acids (16.64 g L-1 ) at 20 days of fermentation. The highest total phenolics were 5.414 g gallic acid equivalent L-1 and total flavonoids 0.617 g rutin equivalent L-1 , as well as the highest DPPH radical scavenging activity (86.19%) and reducing power (0.8802, A700 ) of PSSS fermented at 30 days. Sensory evaluation showed that fermentation of 20 days and 25 days could produce a better taste and aroma of PSSS than 15 days and 30 days. CONCLUSION: PSSS had the highest quality components in the middle of fermentation (20 days) and the highest antioxidant activity in the late fermentation period (30 days). These results demonstrated that peony seed meal could be used to produce high-quality soy sauce with high antioxidant activity. © 2023 Society of Chemical Industry.

The p38-interacting protein p38IP suppresses TCR and LPS signaling by targeting TAK1.

Negative regulation of immunoreceptor signaling is required for preventing hyperimmune activation and maintaining immune homeostasis. The roles of p38IP in immunoreceptor signaling remain unclear. Here, we show that p38IP suppresses T-cell receptor (TCR)/LPS-activated NF-κB and p38 by targeting TAK1 kinase and that p38IP protein levels are downregulated in human PBMCs from rheumatoid arthritis (RA) patients, inversely correlating with the enhanced activity of NF-κB and p38. Mechanistically, p38IP interacts with TAK1 to disassemble the TAK1-TAB (TAK1-binding protein) complex. p38IP overexpression decreases TCR-induced binding of K63-linked polyubiquitin (polyUb) chains to TAK1 but increases that to TAB2, and p38IP knockdown shows the opposite effects, indicating unanchored K63-linked polyUb chain transfer from TAB2 to TAK1. p38IP dynamically interacts with TAK1 upon stimulation, because of the polyUb chain transfer and the higher binding affinity of TAK1 and p38IP for polyUb-bound TAB2 and TAK1, respectively. Moreover, p38IP scaffolds the deubiquitinase USP4 to deubiquitinate TAK1 once TAK1 is activated. These findings reveal a novel role and the mechanisms of p38IP in controlling TCR/LPS signaling and suggest that p38IP might participate in RA pathogenesis.

Protective effects of tree peony seed protein hydrolysate on Cd-induced oxidative damage, inflammation and apoptosis in zebrafish embryos.

The objective of this study was to investigate protective effects of tree peony seed protein hydrolysate by Alcalase (AL-TPSPH) on oxidative damage, inflammation and apoptosis using Cd-induced zebrafish embryos. Zebrafish embryos were treated with either Cd (2 µg/L) or AL-TPSPH (25, 50 and 75 µg/mL) alone or in combination of both from 4 to 144 h post fertilization (hpf). The effects of these treatments on developments, antioxidant parameters and mRNA expression of genes related to oxidative damage, inflammation and apoptosis were examined. The results showed that co-treatment with Cd and AL-TPSPH significantly increased hatching and survival rates and decreased malformation rates of zebrafish embryos compared with Cd treatment alone group (P < 0.05). Cd-induced increase of MDA content, decreases of T-AOC content, GSH/GSSG ratio and activities of SOD, CAT and GPx in zebrafish embryos were modified upon treatment with AL-TPSPH. AL-TPSPH treatment significantly suppressed Cd-induced down-regulations of the antioxidant gene expressions (Mn-sod, Cat and GPx1a) in zebrafish embryos (P < 0.05). AL-TPSPH also prevented Cd-induced up-regulations of pro-inflammatory cytokine (TNF-α, IL-1ß and IFN-γ) expressions. Moreover, AL-TPSPH inhibited Cd-induced up-regulations of pro-apoptotic genes (C-jun, Caspase-3 and Caspase-9) in zebrafish embryos. Collectively, these results indicated that AL-TPSPH could reduce Cd-induced oxidative damage, inflammation and apoptosis in zebrafish embryos, suggesting its future applications as functional food or pharmaceutical ingredient.

The cell structure damage and embden-meyerhof-parnas pathway inhibition of Listeria monocytogenes induced by glycinin basic peptide.

Glycinin basic peptide (GBP) is a natural antibacterial peptide. This study aimed to explore the antibacterial characteristics of GBP against Listeria monocytogenes (L. monocytogenes) by measuring the membrane potential, membrane permeability, cell damage, morphological changes, respiration metabolism inhibition and DNA content. GBP increased the surface zeta potential and decreased the trans-membrane potential of L. monocytogenes in a dose-dependent manner. Compared with the control, the electrical conductivities of GBP-treated bacterial suspensions were significantly increased. The percentages of bacteria with damaged membrane increased from 6.40% to 70.90% with GBP from 0 to 0.8 mg/mL. Obvious rupture and deform of bacterial cells with GBP were observed by transmission electron microscope (TEM), showing the destructive effect of GBP on L. monocytogenes. GBP also inhibited the embden-meyerhof-parnas pathway of the bacterial respiration metabolism and reduced the activities of its key regulator enzymes. Besides, the content of DNA in GBP-treated L. monocytogenes was lower than that in control.

Preparation of polydopamine-coated, graphene oxide/Fe3 O4 - imprinted nanoparticles for selective removal of sulfonylurea herbicides in cereals.

BACKGROUND: Sulfonylureas are potentially toxic broad-spectrum herbicides. They pose a persistent threat to food safety and the environment. It is therefore important to develop a rapid and efficient pretreatment and detection method to prevent their harmful effects on human health. RESULTS: In the present work, a novel and highly selective absorbent for chlorosulfuron (CS) detection was prepared by the simple self-polymerization of dopamine on the surface of magnetic graphene oxide using a CS template. The resultant imprinted nanoparticles (MGO@PDA-MIPs) were characterized by transmission electron microscopy, X-ray diffraction, vibrating-sample magnetometry, thermogravimetric analysis, and nitrogen adsorption-desorption. The adsorption experiments demonstrated that the MGO@PDA-MIPs have excellent selectivity with regard to CS, with a high imprinting factor of 3.41 compared with a non-imprinted polymer. The nanoparticles rapidly achieve adsorption equilibrium and efficient desorption because there are numerous binding sites on the thin polydopamine imprinting layer. Under optimized conditions, the MGO@PDA-MIPs can be used to detect sulfonylurea residues in cereal samples by magnetic solid phase extraction coupled with high performance liquid chromatography (HPLC). The nanoparticles have a satisfactory recovery rate (80.65-101.01%) with a relative standard deviation (RSD) of less than 7.15%, and a limit of detection with regard to CS of 1.61 µg kg-1 (S/N = 3). They can also be re-used at least seven times. CONCLUSION: The MGO@PDA-MIPs have outstanding recognition performance, and can be prepared by a facile, single-step, and environmentally friendly process. They therefore have excellent potential for the recognition and separation of trace sulfonylurea herbicides in complex matrices. © 2020 Society of Chemical Industry.

Characterisation of amphioxus protein kinase C-δ/θ reveals a unique proto-V3 domain suggesting an evolutionary mechanism for PKC-θ unique V3.

A primitive adaptive immune system has recently been suggested to be present in a basal chordate amphioxus (Branchiostoma belcheri, Bb), making it an ideal model for studying the origin of adaptive immune. The novel protein kinase C isoform PKC-θ, but not its closest isoform PKC-δ, plays a critical role for mammalian T-cell activation via translocation to immunological synapse (IS) mediated by a unique PKC-θ V3 domain containing one PxxP motif. To understand the evolution of this unique PKC-θ V3 domain and the primitive adaptive immune system in amphioxus, we comparatively studied the orthologs of PKC-δ and -θ from amphioxus and other species. Phylogenetic analysis showed BbPKC-δ/θ to be the common ancestor of vertebrate PKC-δ and PKC-θ, with a V3 domain containing two PxxP motifs. One motif is conserved in both zebrafish and mammalian PKC-θ but is absent in PKC-δ V3 domain of these species, and has already emerged in drosophila PKC-δ. The other non-conserved motif emerged in BbPKC-δ/θ, and only retained in Danio rerio PKC-δ (DrPKC-δ) but lost in mammalian PKC-δ and -θ. Comparative analyses of the sequence and function of BbPKC-δ/θ, DrPKC-δ, DrPKC-θ and Homo sapiens PKC-θ (HsPKC-θ) in IS translocation and T-cell receptor (TCR)-induced NF-κB activation revealed that retention of the conserved PxxP motif and loss of the non-conserved PxxP motif in mammalian PKC-θ and loss of both PxxP motifs in mammalian PKC-δ accomplish the unique function of PKC-θ in T cells. Together, this study suggests an evolutionary mechanism for PKC-θ unique V3 and reveals BbPKC-δ/θ is the common ancestor of PKC-δ and -θ with a functional proto-V3 domain, supplying new evidence for the existence of primitive adaptive immune system in amphioxus.

Role of nitric oxide and hydrogen sulfide in plant aluminum tolerance.

As gasotransmitter, nitric oxide (NO) and hydrogen sulfide (H2S) are involved in the regulation of plant tolerance to abiotic stresses. Aluminum (Al) toxicity triggers synthesis of NO and H2S and seriously affects plant growth and productivity. Exogenous NO and H2S alleviate Al toxicity in plants. However, the physiological and molecular mechanisms of NO and H2S in alleviating Al toxicity are very scattered. In this review, the advances in the effects of Al on the content of endogenous NO and H2S and the mechanisms of exogenous NO and H2S in alleviating Al toxicity in plants are summarized and discussed. The signaling pathway for the roles of NO and H2S in alleviating Al toxicity is also proposed.

C-R Relationship between Fasting Plasma Glucose and Unfavorable Outcomes in Patients of Ischemic Stroke withoutDiabetes.

BACKGROUND: Limited data are available on the impact of fasting plasma glucose (FPG) on outcomes in nondiabetic acute ischemic stroke patients. METHODS: The prospective, multi-center, and observational study was performed at 8 hospitals in the Liaoning Province between 2015-2016, sought to elucidate the relationship between FPG and the 6-month functional outcomes in nondiabetic acute ischemic stroke patients. The primary effect measure was the adjusted odds ratio for a shift in the direction of unfavorable outcome on the modified Rankin Scale (mRS) score at 6 months, estimated with an ordinal logistic regression, and adjusted for common prognostic factors. Finally, we employed a restricted cubic spline function of linear model to characterize concentration-response (C-R) relationships between FPG and outcomes. RESULTS: A total of 1260 consecutive patients were enrolled, 48.9% of patients had FPG levels >6.1mmol/L. A total of 282 (22.4%) patients achieved an unfavorable neurologic outcome. Patients achieving an unfavorable neurologic outcome had significantly higher levels of FPG than those achieving a favorable neurologic outcome (6.47mmol/L versus 7.02 mmol/L). FPG was significantly related to an unfavorable neurologic outcome in nondiabetic acute ischemic stroke patients. The C-R curve showed a nonlinear relation between FPG and 6-month mRS with the nadir at 5.9mmol/L. Moreover, the likelihood of unfavorable outcome increased by 8.5% for each 1mmol/L increase in FPG. CONCLUSIONS: Early identification and prompt hyperglycemia management should be considered to improve the functional outcomes during the early poststroke stage.