CAFs-derived exosomes promote the development of cervical cancer by regulating miR-18a-5p-TMEM170B signaling axis.

Mounting studies have showed that tumor microenvironment (TME) is crucial for cervical cancer (CC), and cancer-related fibroblasts (CAFs) play a major role in it. Recently, exosomal miRNAs secreted by CAFs have been found to be potential targets for cancer diagnosis and therapy. In this paper, we aimed to investigate the function of CAFs-mediated exosome miR-18a-5p (CAFs-exo-miR-18a-5p) in CC. First, in combination with bioinformatic data analysis of the GEO database (GSE86100) and RT-qPCR of CC clinical tissue samples and cell lines, miR-18a-5p was discovered to be markedly up-regulated in CC. Next, CAFs-secreted exosomes were isolated and it was found that miR-18a-5p expression was dramatically promoted in CC cell lines when treated with CAFs-exos. The CAFs-exo-miR-18a-5p was then elucidated to stimulate the proliferation and migration and inhibit the apoptosis of CC cells. In order to clarify the underlying mechanism, we further screened the target genes of miR-18a-5p. TMEM170B was selected by bioinformatic data analysis of online databases combined with RT-qPCR of CC clinical tissues and cells. Luciferase reporter gene analysis combined with molecular biology experiments further elucidated that miR-18a-5p suppressed TMEM170B expression in CC. Finally, both cell and animal experiments demonstrated that TMEM170B over-expression attenuated the oncogenic effect of CAFs-exo-miR-18a-5p. In conclusion, our study indicates that CAFs-mediated exosome miR-18a-5p promotes the initiation and development of CC by suppressing TMEM170B signaling axis, which provides a possible direction for the diagnosis and therapy of CC.

d-p Hybridization-Induced "Trapping-Coupling-Conversion" Enables High-Efficiency Nb Single-Atom Catalysis for Li-S Batteries.

Single-atom catalysts have been paid more attention to improving sluggish reaction kinetics and anchoring polysulfide for lithium-sulfur (Li-S) batteries. It has been demonstrated that d-block single-atom elements in the fourth period can chemically interact with the local environment, leading to effective adsorption and catalytic activity toward lithium polysulfides. Enlightened by theoretical screening, for the first time, we design novel single-atom Nb catalysts toward improved sulfur immobilization and catalyzation. Calculations reveal that Nb-N4 active moiety possesses abundant unfilled antibonding orbitals, which promotes d-p hybridization and enhances anchoring capability toward lithium polysulfides via a "trapping-coupling-conversion" mechanism. The Nb-SAs@NC cell exhibits a high capacity retention of over 85% after 1000 cycles, a superior rate performance of 740 mA h g-1 at 7 C, and a competitive areal capacity of 5.2 mAh cm-2 (5.6 mg cm-2). Our work provides a new perspective to extend cathodes enabling high-energy-density Li-S batteries.

De novo design of dual-target JAK2, SMO inhibitors based on deep reinforcement learning, molecular docking and molecular dynamics simulations.

Triple-negative breast cancer (TNBC) and HER2-positive breast cancer are particularly aggressive and the effectiveness of current therapies for them is limited. TNBC lacks effective therapies and HER2-positive cancer is often resistant to HER2-targeted drugs after an initial response. The recent studies have demonstrated that the combination of JAK2 inhibitors and SMO inhibitors can effectively inhibit the growth and metastasis of TNBC and HER2-positive drug resistant breast cancer cells. In this study, deep reinforcement learning was used to learn the characteristics of existing small molecule inhibitors of JAK2 and SMO, and to generate a novel library of small molecule compounds that may be able to inhibit both JAK2 and SMO. Subsequently, the molecule library was screened by molecular docking and a total of 7 compounds were selected out as dual inhibitors of JAK2 and SMO. Molecular dynamics simulations and binding free energies showed that the top three compounds stably bound to both JAK2 and SMO proteins. The binding free energies and hydrogen bond occupancy of key amino acids indicate that A8976 and A10625 has good properties and could be a potential dual-target inhibitor of JAK2 and SMO.

Tailoring the p-Band Center of NS Pair for Accelerating High-Performance Lithium-Oxygen Battery.

The local coordination environment of catalytical moieties directly determines the performance of electrochemical energy storage and conversion devices, such as Li-O2 batteries (LOBs) cathode. However, understanding how the coordinative structure affects the performance, especially for non-metal system, is still insufficient. Herein, a strategy that introduces S-anion to tailor the electronic structure of nitrogen-carbon catalyst (SNC) is proposed to improve the LOBs performance. This study unveils that the introduced S-anion effectively manipulates the p-band center of pyridinic-N moiety, substantially reducing the battery overpotential by accelerating the generation and decomposition of intermediate products Li1-3 O4 . The lower adsorption energy of discharging product Li2 O2 on NS pair accounts for the long-term cyclic stability by exposing the high active area under operation condition. This work demonstrates an encouraging strategy to enhance LOBs performance by modulating the p-band center on non-metal active sites.

DNA Helix Structure Inspired Flexible Lithium-Ion Batteries with High Spiral Deformability and Long-Lived Cyclic Stability.

With the development of flexible devices, it is necessary to design high-performance power supplies with superior flexibility, durability, safety, etc., to ensure that they can be deformed with the device while retaining their electrochemical functions. Herein, we have designed a flexible lithium-ion battery inspired by the DNA helix structure. The battery structure is mainly composed of multiple thick energy stacks for energy storage and some grooves for stress buffers, which realized the spiral deformation of batteries. According to the results, the batteries exhibit less than 3% capacity degradation even after more than 31000 times of in situ dynamic mechanical loadings. Moreover, the mechanism of the battery with spiral deformability is further revealed. It is anticipated that this bioinspired design strategy could create unique opportunities for the commercialization of flexible batteries and fill the current gap in realizing battery-specific deformations to meet various requirements for future complex device designs.

Kirigami-Inspired Flexible Lithium-Ion Batteries via Transformation of Concentrated Stress into Segmented Strain.

Emerging directions in the growing wearable electronics market have spurred the development of flexible energy storage systems that require deformability while maintaining electrochemical performance. However, the traditional fabrication approaches of lithium-ion batteries (LIBs) are challenging to withstand long-cycle bending alternating loads due to the stress concentration caused by the nonuniformity of the actual deformation. Herein, inspired by kirigami, a segmented deformation design of full-cell scale thin-type flexible lithium-ion batteries (FLIBs) with large-scale manufacturing characteristics via the current collector's mechanical blanking process is reported. This strategy allows the battery's elliptical deformation of the actual state to be transformed into the circular strain of the ideal configuration, thereby dispersing the stress concentration on the top of the battery. According to the results, the designed battery maintains >95% capacity after >20 000 harsh in situ dynamic tests. In addition, finite element analysis further reveals the mechanism that the segmented deformation strategy bears the mechanical stress. This work can enlighten the rational design and customization of electrode patterns for high compatibility with various devices, thereby providing potential opportunities for the application of FLIBs.

Single-Atom Tailored Hierarchical Transition Metal Oxide Nanocages for Efficient Lithium Storage.

Mitigating the mechanical degradation and enhancing the ionic/electronic conductivity are critical but challengeable issues toward improving electrochemical performance of conversion-type anodes in rechargeable batteries. Herein, these challenges are addressed by constructing interconnected 3D hierarchically porous structure synergistic with Nb single atom modulation within a Co3 O4 nanocage (3DH-Co3 O4 @Nb). Such a hierarchical-structure nanocage affords several fantastic merits such as rapid ion migration and enough inner space for alleviating volume variation induced by intragrain stress and optimized stability of the solid-electrolyte interface. Particularly, experimental studies in combination with theoretical analysis verify that the introduction of Nb into the Co3 O4 lattice not only improves the electron conductivity, but also accelerates the surface/near-surface reactions defined as pesudocapacitance behavior. Dynamic behavior reveals that the ensemble design shows huge potential for fast and large lithium storage. These features endow 3DH-Co3 O4 @Nb with remarkable battery performance, delivering ≈740 mA h g-1 after ultra-long cycling of 1000 times under a high current density of 5 A g-1 . Importantly, the assembled 3DH-Co3 O4 @Nb//LiCoO2 pouch cell also presents a long-lived cycle performance with only ≈0.059% capacity decay per cycle, inspiring the design of electrode materials from both the nanostructure and atomic level toward practical applications.

Candidates for chemosensory genes identified in the Chinese citrus fly, Bactrocera minax, through a transcriptomic analysis.

BACKGROUND: The males of many Bactrocera species (Diptera: Tephritidae) respond strongly to plant-derived chemicals (male lures) and can be divided into cue lure/raspberry ketone (CL/RK) responders, methyl eugenol (ME) responders and non-responders. Representing a non-responders, Bactrocera minax display unique olfactory sensory characteristics compared with other Bactrocera species. The chemical senses of insects mediate behaviors that are associated with survival and reproduction. Here, we report the generation of transcriptomes from antennae and the rectal glands of both male and female adults of B. minax using Illumina sequencing technology, and annotated gene families potentially responsible for chemosensory. RESULTS: We developed four transcriptomes from different tissues of B. minax and identified a set of candidate genes potentially responsible for chemosensory by analyzing the transcriptomic data. The candidates included 40 unigenes coding for odorant receptors (ORs), 30 for ionotropic receptors (IRs), 17 for gustatory receptors (GRs), three for sensory neuron membrane proteins (SNMPs), 33 for odorant-binding proteins (OBPs), four for chemosensory proteins (CSPs). Sex- and tissue-specific expression profiles for candidate chemosensory genes were analyzed via transcriptomic data analyses, and expression profiles of all ORs and antennal IRs were investigated by real-time quantitative PCR (RT-qPCR). Phylogenetic analyses were also conducted on gene families and paralogs from other insect species together. CONCLUSIONS: A large number of chemosensory genes were identified from transcriptomic data. Identification of these candidate genes and their expression profiles in various tissues provide useful information for future studies towards revealing their function in B. minax.

Role of Methylprednisolone in Treatment of Spinal Cord Injured with Bone Marrow Mesenchymal Stem Cells Transplantation in Rats and Its Effect on the Expressions of Tumor Necrosis Factor-α and Interleukin-1ß.

Objective To investigate the role of methylprednisolone (MP) in treatment of spinal cord injured (SCI) with bone marrow mesenchymal stem cells (BMSCs) transplantation in rats and its effect on the expressions of tumor necrosis factor-α(TNF-α) and interleukin-1ß(IL-1ß) at the local tissues.Methods Forty male Sprague-Dawley(SD) rats were used to establish the models of SCI according to the modified Allen's contusion method and then divided into four groups (n=10 in each group) by using random numbers table:MP group,BMSCs group,BMSCs+MP group,and control group.MP was intravenously administrated immediately after SCI.BMSCs labeled by 5-bromo-2-deoxyuridine(BrdU)were transplanted into the injured sites of spinal cord after two hours of SCI.On the 1 st,7 th,and 14th days after SCI,when functional outcome measurements were evaluated by the Basso-Beattie-Bresnahan (BBB) score.On the 14th day after treatment,the spine cord tissues were harvested for the TNF-α/IL-1ß immunohistochemistry,and Tunel staining method was used to detect cell apoptosis rate.BrdU-positive BMSCs were examined in BMSCs group and BMSCs+MP group.Results Functional recovery of hind limb in MP+BMSCs group was the best among the four group.On the 1 st day after injury,the BBB scores showed no significant difference among four group(χ2=1.0756,P=0.7829).On the 7th and 14th day,the BBB score of MP+BMSCs group was significantly higher than MP group (χ2=17.7186,P=0.0002;χ2= 24.7259,P<0.0001) and BMSCs group (χ2=15.8110,P=0.0024;χ2=25.6014,P<0.0001),respectively.The BBB score of the control group was significantly lower than MP group (χ2=8.3265,P=0.0325;χ2=13.5060,P=0.0062) and BMSCs group (χ2=14.1166,P=0.0036;χ2=8.9613,P=0.0299),respectively.On the 14th day,immunohistochemical staining presented that the TNF-α and IL-1ß-positive cells in MP+BMSCs group were significantly lower than MP group (q=5.573,P=0.0004;q=4.596,P=0.0025) and BMSCs group (q=13.780,P<0.0001;q=8.456,P<0.0001),and control group was significantly higher than MP group (q=14.710,P<0.0001;q=6.710,P<0.0001) and BMSCs group (q=6.502,P=0.0001;q=2.849,P=0.0514).Tunel staining showed the apoptotic rate of spinal cord cells in four group were (48.47±5.70)%,(31.95±3.58)%,(41.39±2.33)%,and (23.48±2.69)%.The number of apoptotic cells in MP+BMSCs group was least in four groups;compared with the control group,the apoptotic rate significantly decreased in MP group (q=14.840,P<0.0001) and BMSCs group (q=6.716,P=0.0002);compared with the MP+BMSCs group,the apoptotic rate was significantly increased in the MP group (q=7.332,P=0.0001) and BMSCs group (q=15.460,P<0.0001). BrdU staining revealed BrdU-positive rate in MP+BMSCs group [(9.3000±0.5175)%] was significantly higher than that in BMSCs group [(6.6000±0.3399)%](t=4.361,P=0.0004).Conclusion MP can improve the function of the hind limbs of SCI rats treated with BMSCs transplantation and lower the expressions of TNF-α and IL-1ß in injured tissue.

QSAR and molecular docking studies on oxindole derivatives as VEGFR-2 tyrosine kinase inhibitors.

The three-dimensional quantitative structure-activity relationships (3D-QSAR) were established for 30 oxindole derivatives as vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitors by using comparative molecular field analysis (CoMFA) and comparative similarity indices analysis comparative molecular similarity indices analysis (CoMSIA) techniques. With the CoMFA model, the cross-validated value (q(2)) was 0.777, the non-cross-validated value (R(2)) was 0.987, and the external cross-validated value ([Formula: see text]) was 0.72. And with the CoMSIA model, the corresponding q(2), R(2) and [Formula: see text] values were 0.710, 0.988 and 0.78, respectively. Docking studies were employed to bind the inhibitors into the active site to determine the probable binding conformation. The binding mode obtained by molecular docking was in good agreement with the 3D-QSAR results. Based on the QSAR models and the docking binding mode, a set of new VEGFR-2 tyrosine kinase inhibitors were designed, which showed excellent predicting inhibiting potencies. The result revealed that both QSAR models have good predictive capability to guide the design and structural modification of homologic compounds. It is also helpful for further research and development of new VEGFR-2 tyrosine kinase inhibitors.

Generic and accurate prediction of retention times in liquid chromatography by post-projection calibration.

Retention time predictions from molecule structures in liquid chromatography (LC) are increasingly used in MS-based targeted and untargeted analyses, providing supplementary evidence for molecule annotation and reducing experimental measurements. Nevertheless, different LC setups (e.g., differences in gradient, column, and/or mobile phase) give rise to many prediction models that can only accurately predict retention times for a specific chromatographic method (CM). Here, a generic and accurate method is present to predict retention times across different CMs, by introducing the concept of post-projection calibration. This concept builds on the direct projections of retention times between different CMs and uses 35 external calibrants to eliminate the impact of LC setups on projection accuracy. Results showed that post-projection calibration consistently achieved a median projection error below 3.2% of the elution time. The ranking results of putative candidates reached similar levels among different CMs. This work opens up broad possibilities for coordinating retention times between different laboratories and developing extensive retention databases.

Regulating the Solvation Shell Structure of Lithium Ions for Smooth Li Metal Deposition in Quasi-Solid-State Batteries.

Gel polymer electrolytes (GPE) are promising next-generation electrolytes for high-energy batteries, combining the multiple advantages of liquid and all-solid-state electrolytes. Herein, we a synthesized GPE using poly(ethylene glycol)acrylate (PEGDA) in order to understand how the GPE efficiently inhibits lithium dendrite formation and growth. The effects of PEGDA on the solvation shell structure of the lithium ion are investigated using density functional theory (DFT) and ab initio molecular dynamics (AIMD) simulations, which are also supported by Raman spectroscopy. The GPE electrolytes with optimal PEGDA concentration exhibit high transference numbers (t Li + ${{_{{\rm Li}{^{+}}}}}$ =0.72) and ionic conductivity (σ=3.24 mS cm-1 ). A symmetric lithium ion battery using GPE can be stably cycled for 1200 h in comparison to 320 h in a liquid electrolyte (LE), possibly owing to the high content of LiF (17.9 %) in the solid-electrolyte interphase film of the GPE cell. The observed concentration/electric field gradient observed through the finite element method also accounts for the good cycling performance. In addition, a LiCoO2 |GPE|Li cell demonstrates excellent capacity retention of 87.09 % for 200 cycles; this approach could present promising guidelines for the design of high-energy lithium batteries.

Discovery and design of dual inhibitors targeting Sphk1 and Sirt1.

CONTEXT: Leukaemia has become a serious threat to human health. Although tyrosine kinase inhibitors (TKIs) have been developed as targets for the remedy of leukaemia, drug resistance occurs. Research demonstrated that the simultaneous targeting of sphingosine kinase 1 (Sphk1) and Sirtuin 1 (Sirt1) can downregulate myeloid cell leukaemia-1 (MCL-1), overcome the resistance of tyrosine kinase inhibitors, and play a synergistic inhibitory impact on leukaemia treatment. METHODS: In this study, virtual screening of 7.06 million small molecules was done by sphingosine kinase 1 and Sirtuin 1 pharmacophore models using Schrödinger version 2019; after that, ADME and Toxicity molecule properties were predicted using Discovery Studio. Molecular docking using Schrödinger selected five molecules, which have the best binding affinity with sphingosine kinase 1 and Sirtuin 1. The five molecules and reference inhibitors were constructed with a total of 12 systems with GROMACS that carried out 100 ns molecular dynamics simulation and molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) calculation. Due to compound 3 has the lowest binding energy, its structure was modified. A series of compounds docked with sphingosine kinase 1 and Sirtuin 1, respectively. Among them, QST-LC03, QST-LD05, QST-LE03, and QST-LE04 have the better binding affinity than reference inhibitors. Moreover, the SwissADME and PASS platforms predict that 1, 3, QST-LC03, and QST-LE04 have further study value.

Crop cultivation planning with fuzzy estimation using water wave optimization.

In a complex agricultural region, determine the appropriate crop for each plot of land to maximize the expected total profit is the key problem in cultivation management. However, many factors such as cost, yield, and selling price are typically uncertain, which causes an exact programming method impractical. In this paper, we present a problem of crop cultivation planning, where the uncertain factors are estimated as fuzzy parameters. We adapt an efficient evolutionary algorithm, water wave optimization (WWO), to solve this problem, where each solution is evaluated based on three metrics including the expected, optimistic and pessimistic values, the combination of which enables the algorithm to search credible solutions under uncertain conditions. Test results on a set of agricultural regions in East China showed that the solutions of our fuzzy optimization approach obtained significantly higher profits than those of non-fuzzy optimization methods based on only the expected values.

Electrolyte-assisted low-voltage decomposition of Li2C2O4 for efficient cathode pre-lithiation in lithium-ion batteries.

Lithium oxalate (Li2C2O4) is an attractive cathode pre-lithiation additive for lithium-ion batteries (LIBs), but its application is hindered by its high decomposition potential (>4.7 V). Due to the liquid-solid synergistic effect of the NaNO2 additive and the LiNi0.83Co0.07Mn0.1O2 (NCM) cathode material, the decomposition efficiency of micro-Li2C2O4 reaches 100% at a low charge cutoff voltage of 4.3 V. Our work boosts the widespread practical application of Li2C2O4 by a simple and promising electrolyte-assisted cathode pre-lithiation strategy.

[Screening of organophosphorus flame retardant residues in rice by QuEChERS-gas chromatography-quadrupole time-of-flight mass spectrometry].

Organophosphorus flame retardants (OPFRs) have emerged as good alternatives to brominated flame retardants, the use of which is globally restricted. In this study, a screening method based on QuEChERS-gas chromatography-quadrupole time-of-flight mass spectrometry (GC-Q-TOF/MS) was established for the determination of 21 OPFRs in rice. First, full scan (scanning range, m/z 50-450) was performed with a mixed standard solution of the 21 OPFRs (0.1 µg/g) by GC-Q-TOF/MS. The fragmentation pathways of these OPFRs were then investigated to explore their cleavage fragments, the interrelationships among fragments, and the possible cleavage modes of alkylated, chlorinated, and aromatic OPFRs. The retention times, isotopic abundance ratios, and molecular formulas of the characteristic fragments as well as the exact mass of the compounds were obtained to establish a mass spectral library of the OPFRs. Rice samples were extracted and purified by the QuEChERS method, and 0.5% formate acetonitrile solution was used as the extraction solvent; 4 g of magnesium sulfate, 1 g of sodium chloride, 0.5 g of disodium hydrogen citrate, and 1 g of sodium citrate as the extraction-salt combination; and 50 mg of primary secondary amine (PSA), 50 mg of octadecylsilane (C18), and 150 mg of magnesium sulfate as the purification materials. The chromatographic separation of the 21 OPFRs was completed within 16 min under optimized temperature program conditions on the DB-5MS UI column. The screening parameters were optimized, and a full scan of the samples was performed under the following conditions: number of characteristic fragment ions ≥2; accurate mass window=±2×10-5 (±20 ppm); retention time deviation=±0.2 min, and ion abundance deviation<20%. The developed method was applied to the screening 21 OPFRs in the samples. The results indicated that the matrix interference was greatly reduced by decreasing the extraction accurate mass window, thereby improving the signal-to-noise ratio of the analytes. The targets were extracted from the matrix interference and background noise using deconvolution software, which improved the match between the target compounds and the mass spectral library. The detection rates of alkyl and aromatic OPFRs increased by 22% and 25%, respectively, when the spiking level was increased from 2 to 10 ng/g. Among the chlorinated OPFRs, only tris(2-chloroisopropyl) phosphate (TCIPP) was not detected at a spiking level of 2 ng/g, indicating that chlorinated OPFRs could be identified even at low concentrations. The characteristic ions of the detected compounds matched those of the home-made mass spectral library well, indicating that the practical application of the home-made mass spectral library. The established screening method was applied in the determination of OPFRs in rice samples from different regions in China. A total of 11 OPFRs were detected, among which trimethyl phosphate (TMP), tri-iso-butyl phosphate (TiBP), and tris(3,5-dimethylphenyl) phosphate (T35DMPP) had the highest detection rates. These results indicate that these three OPFRs are widely used and can easily come into contact with rice samples through various routes. Differences in the types of OPFRs detected in the actual samples may be related to the types of OPFRs produced in local factories. OPFRs can be detected in rice samples by the developed GC-Q-TOF/MS screening method, which is helpful for the identification of OPFRs in complex matrix samples.

Design of SARS-CoV-2 Mpro, PLpro dual-target inhibitors based on deep reinforcement learning and virtual screening.

Background: Since December 2019, SARS-CoV-2 has continued to spread rapidly around the world. The effective drugs may provide a long-term strategy to combat this virus. The main protease (Mpro) and papain-like protease (PLpro) are two important targets for the inhibition of SARS-CoV-2 virus replication and proliferation. Materials & methods: In this study, deep reinforcement learning, covalent docking and molecular dynamics simulations were used to identify novel compounds that have the potential to inhibit both Mpro and PLpro. Results & conclusion: Three compounds were identified that can effectively occupy the Mpro protein cavity with the PLpro protein cavity and form high-frequency contacts with key amino acid residues (Mpro: His41, Cys145, Glu166; PLpro: Cys111). These three compounds can be further investigated as potential lead compounds for SARS-CoV-2 inhibitors.

Identification and Expression Analyses of Olfactory Gene Families in the Rice Grasshopper, Oxya chinensis, From Antennal Transcriptomes.

The rice grasshopper Oxya chinensis is an important agricultural pest of rice and other gramineous plants. Chemosensory genes are crucial factors in direct interactions with odorants in the olfactory process. Here we identified genes encoding 18 odorant-binding proteins (OBPs), 13 chemosensory proteins (CSPs), 94 olfactory receptors (ORs), 12 ionotropic receptors (IRs), and two sensory neuron membrane proteins (SNMPs) from O. chinensis using an transcriptomic approach. Semi-quantitative RT-PCR assays revealed that six OBP-encoding genes (OchiOBP4, 5, 8, 9, 10, and 14), one CSP gene (OchiOBP10) and two IR genes (OchiIR28 and 29) were exclusively expressed in antennae, suggesting their roles in olfaction. Real-time quantitative PCR analyses revealed that genes expressed exclusively or predominantly in antennae also displayed significant differences in expression levels between males and females. Among the differentially expressed genes, 17 OR-encoding genes, one CSP- and one SNMP-gene showed female-biased expression, suggesting that they may be involved in some female-specific behaviors such as seeking oviposition site; whereas the three remaining OR-encoding genes showed male-biased expression, indicating their possible roles in sensing female sex pheromones. Our results laid a solid foundation for future studies to reveal olfactory mechanisms as well as designing strategies for controlling this rice pest.

Selection of Reference Genes for Optimal Normalization of Quantitative Real-Time Polymerase Chain Reaction Results for Diaphorina citri Adults.

The Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Liviidae), can cause direct damage to citrus trees and is the main vector for the devastating disease, citrus greening disease or huanglongbing. Most molecular studies on this important insect pest use real-time reverse-transcription quantitative polymerase chain reaction (RT-qPCR) to quantify gene expression, including analyzing molecular basis for insecticide resistance in field populations. One critical factor to cause inaccuracy in RT-qPCR results is the lack of appropriate internal reference genes for optimal data normalization. In this study, the expression levels of 10 selected reference genes were evaluated in different tissue samples of psyllid adults and in the insects treated with different temperatures and insecticides. Data were analyzed using different computational algorithms, including Delta Ct, BestKeeper, NormFinder, geNorm, and RefFinder. According to our results, at least two reference genes should be used for the normalization of RT-qPCR data in this insect. The best choices of reference genes for different samples are as follows: ACT1 and Ferritin for different tissue samples, RPS20 and Ferritin for samples treated with different temperatures, TBP and EF1α for samples treated with imidacloprid, and Ferritin and TBP for samples treated with beta-cypermethrin. The reference genes identified in this study should be useful for future studies to analyze the expression patterns of target genes, especially for genes linked with temperature adaptability and insecticide resistance in this insect species in the future.

FKBP family proteins: immunophilins with versatile biological functions.

Immunophilins consist of a family of highly conserved proteins binding with immunosuppressive drugs such as FK506, rapamycin and cyclosporin A. FK506-binding protein (FKBP) is one of two major immunophilins and most of FKBP family members bind FK506 and show peptidylprolyl cis/trans isomerase (PPIase) activity. Small size FKBP family members contain only FK506-binding domain, while FKBPs with large molecular weights possess extra domains such as tetratricopeptide repeat domains, calmodulin binding and transmembrane motifs. FKBPs are involved in several biochemical processes including protein folding, receptor signaling, protein trafficking and transcription. FKBP family proteins play important functional roles in the T-cell activation, when complexed with their ligands. The roles of immunophilins in protein transportation and apoptosis through their molecular interactions with receptors or proteins have emerged recently. Moreover, therapeutic implications of immunophilin ligands in treating neurodegenerative disorders have been accumulating. FK506 and its derivatives with no immunosuppressive activities bind to the conserved active sites of the canonical FKBP members such as FKBP12, which shows PPIase activity. These immunophilin ligands show variable efficacy in animal models for Parkinson's disease, dementia, and spinal cord injury, where the canonical immunophilins function as chaperones and are associate with the protein folding and modulation of oxidative stress. On the other hand, in the noncanonical FKBP members such as FKBP38, FK506-binding site is not conserved and shows neither PPIase activity nor affinity to FK506. Interestingly, the small molecule-mediated inhibition of the noncanonical member of FKBP family appears to cause neuronal protection and induce proliferation of neuronal stem cells in a rat focal cerebral ischemia model. Currently, the mechanisms of actions remain unclear. This review focuses on molecular characteristics of the canonical and noncanonical FKBP family members and the biological functions of their ligands in performing neuroprotective and neurotrophic activities.