A lateral flow strip for on-site detection of homocysteine based on a truncated aptamer.

An elevated level of homocysteine (Hcy) in serum is closely related to the development of various diseases. Therefore, homocysteine has been widely employed as a biomarker in medical diagnosis and the on-site detection of homocysteine is highly desired. In this study, a truncated highly specific aptamer for homocysteine was screened and used to design a lateral flow strip (LFS) for the detection of homocysteine. The aptamer was derived from a previously reported sequence. Based on the result of molecular docking, the original sequence was subjected to truncation, resulting in a reduction of the length from 66 nt to 55 nt. Based on the truncated aptamer, the LFS was designed for the detection of homocysteine. In the presence of homocysteine, the aptamer selectively binds to it, releasing cDNA from the aptamer/cDNA duplex. This allows cDNA to bind to the capture probe immobilized on the T zone of the strip, resulting in a red signal on the T zone from gold nanoparticles (AuNPs). The strip enables the visual detection of homocysteine in 5 min. Quantitative detection can be facilitated with the aid of ImageJ software. In this mode, the linear detection range for homocysteine is within 5-50 µM, with a detection limit of 4.18 µM. The strip has been effectively utilized for the detection of homocysteine in human serum. Consequently, the combination of the truncated aptamer and the strip offers a method that is sensitive, quick, and economical for the on-site detection of homocysteine.

Metabolite Study and Structural Authentication for the First-in-Human Use Sphingosine-1-phosphate Receptor 1 Radiotracer.

The sphingosine-1-phosphate receptor 1 (S1PR1) radiotracer [11C]CS1P1 has shown promise in proof-of-concept PET imaging of neuroinflammation in multiple sclerosis (MS). Our HPLC radiometabolite analysis of human plasma samples collected during PET scans with [11C]CS1P1 detected a radiometabolite peak that is more lipophilic than [11C]CS1P1. Radiolabeled metabolites that cross the blood-brain barrier complicate quantitative modeling of neuroimaging tracers; thus, characterizing such radiometabolites is important. Here, we report our detailed investigation of the metabolite profile of [11C]CS1P1 in rats, nonhuman primates, and humans. CS1P1 is a fluorine-containing ligand that we labeled with C-11 or F-18 for preclinical studies; the brain uptake was similar for both radiotracers. The same lipophilic radiometabolite found in human studies also was observed in plasma samples of rats and NHPs for CS1P1 labeled with either C-11 or F-18. We characterized the metabolite in detail using rats after injection of the nonradioactive CS1P1. To authenticate the molecular structure of this radiometabolite, we injected rats with 8 mg/kg of CS1P1 to collect plasma for solvent extraction and HPLC injection, followed by LC/MS analysis of the same metabolite. The LC/MS data indicated in vivo mono-oxidation of CS1P1 produces the metabolite. Subsequently, we synthesized three different mono-oxidized derivatives of CS1P1 for further investigation. Comparing the retention times of the mono-oxidized derivatives with the metabolite observed in rats injected with CS1P1 identified the metabolite as N-oxide 1, also named TZ82121. The MS fragmentation pattern of N-oxide 1 also matched that of the major metabolite in rat plasma. To confirm that metabolite TZ82121 does not enter the brain, we radiosynthesized [18F]TZ82121 by the oxidation of [18F]FS1P1. Radio-HPLC analysis confirmed that [18F]TZ82121 matched the radiometabolite observed in rat plasma post injection of [18F]FS1P1. Furthermore, the acute biodistribution study in SD rats and PET brain imaging in a nonhuman primate showed that [18F]TZ82121 does not enter the rat or nonhuman primate brain. Consequently, we concluded that the major lipophilic radiometabolite N-oxide [11C]TZ82121, detected in human plasma post injection of [11C]CS1P1, does not enter the brain to confound quantitative PET data analysis. [11C]CS1P1 is a promising S1PR1 radiotracer for detecting S1PR1 expression in the CNS.

Efficient and Robust Point Cloud Registration via Heuristics-guided Parameter Search.

Estimating the rigid transformation with 6 degrees of freedom based on a putative 3D correspondence set is a crucial procedure in point cloud registration. Existing correspondence identification methods usually lead to large outlier ratios (> 95% is common), underscoring the significance of robust registration methods. Many researchers turn to parameter search-based strategies (e.g., Branch-and-Bround) for robust registration. Although related methods show high robustness, their efficiency is limited to the high-dimensional search space. This paper proposes a heuristics-guided parameter search strategy to accelerate the search while maintaining high robustness. We first sample some correspondences (i.e., heuristics) and then just need to sequentially search the feasible regions that make each sample an inlier. Our strategy largely reduces the search space and can guarantee accuracy with only a few inlier samples, therefore enjoying an excellent trade-off between efficiency and robustness. Since directly parameterizing the 6-dimensional nonlinear feasible region for efficient search is intractable, we construct a three-stage decomposition pipeline to reparameterize the feasible region, resulting in three lower-dimensional sub-problems that are easily solvable via our strategy. Besides reducing the searching dimension, our decomposition enables the leverage of 1-dimensional interval stabbing at all three stages for searching acceleration. Moreover, we propose a valid sampling strategy to guarantee our sampling effectiveness, and a compatibility verification setup to further accelerate our search. Extensive experiments on both simulated and real-world datasets demonstrate that our approach exhibits comparable robustness with state-of-the-art methods while achieving a significant efficiency boost.

Engineered hsa-miR-455-3p-Abundant Extracellular Vesicles Derived from 3D-Cultured Adipose Mesenchymal Stem Cells for Tissue-Engineering Hyaline Cartilage Regeneration.

Efforts are made to enhance the inherent potential of extracellular vesicles (EVs) by utilizing 3D culture platforms and engineered strategies for functional cargo-loading. Three distinct types of adipose mesenchymal stem cells-derived EVs (ADSCs-EVs) are successfully isolated utilizing 3D culture platforms consisting of porous gelatin methacryloyl (PG), PG combined with sericin methacryloyl (PG/SerMA), or PG combined with chondroitin sulfate methacryloyl (PG/ChSMA). These correspond to PG-EVs, PG/SerMA-EVs, and PG/ChSMA-EVs, respectively. Unique microRNA (miRNA) profiles are observed in each type of ADSCs-EVs. Notably, PG-EVs encapsulate higher levels of hsa-miR-455-3p and deliver more hsa-miR-455-3p to chondrocytes, which results in the activation of the hsa-miR-455-3p/PAK2/Smad2/3 axis and the subsequent hyaline cartilage regeneration. Furthermore, the functionality of PG-EVs is optimized through engineered strategies, including agomir/lentivirus transfection, electroporation, and Exo-Fect transfection. These strategies, referred to as Agomir-EVs, Lentivirus-EVs, Electroporation-EVs, and Exo-Fect-EVs, respectively, are ranked based on their efficacy in encapsulating hsa-miR-455-3p, delivering hsa-miR-455-3p to chondrocytes, and promoting cartilage formation via the hsa-miR-455-3p/PAK2/Smad2/3 axis. Notably, Exo-Fect-EVs exhibit the highest efficiency. Collectively, the 3D culture conditions and engineered strategies have an impact on the miRNA profiles and cartilage regeneration capabilities of ADSCs-EVs. The findings provide valuable insights into the mechanisms underlying the promotion of cartilage regeneration by ADSCs-EVs.

piRNA loading triggers MIWI translocation from the intermitochondrial cement to chromatoid body during mouse spermatogenesis.

The intermitochondrial cement (IMC) and chromatoid body (CB) are posited as central sites for piRNA activity in mice, with MIWI initially assembling in the IMC for piRNA processing before translocating to the CB for functional deployment. The regulatory mechanism underpinning MIWI translocation, however, has remained elusive. We unveil that piRNA loading is the trigger for MIWI translocation from the IMC to CB. Mechanistically, piRNA loading facilitates MIWI release from the IMC by weakening its ties with the mitochondria-anchored TDRKH. This, in turn, enables arginine methylation of MIWI, augmenting its binding affinity for TDRD6 and ensuring its integration within the CB. Notably, loss of piRNA-loading ability causes MIWI entrapment in the IMC and its destabilization in male germ cells, leading to defective spermatogenesis and male infertility in mice. Collectively, our findings establish the critical role of piRNA loading in MIWI translocation during spermatogenesis, offering new insights into piRNA biology in mammals.

MXene-mediated Interfacial Growth of 2D-2D Heterostructured Nanomaterials as Cathodes for Zn-based Aqueous Batteries.

In this study, we introduce a novel approach for synthesizing two-dimensional (2D) MXene heterostructures featuring a sandwiched and cross-linked network structure. This method addresses the common issue of activity degradation in 2D nanomaterials caused by inevitable aggregation. By utilizing the distinct surface characteristics of MXene, we successfully induced the growth of various 2D nanomaterials on MXene substrates. This strategy effectively mitigates self-stacking defects and augments the exposure of surface areas. In particular, the obtained 2D-2D MXene@NiCo-layered double hydroxide (MH-NiCo) heterostructures exhibit enhanced structural stability, improved chemical reversibility, and heightened charge transfer efficiency, outperforming pure NiCo LDH. The aqueous MH-Ni4Co1//Zn@carbon cloth (MH-Ni4Co1//Zn@CC) battery demonstrates exceptional performance with a remarkable specific capacity of 0.61 mAh cm-2, maintaining 96.6 % capacitance after 2300 cycles. Additionally, it achieves an energy density of 1.047 mWh cm-2 and a power density of 32.899 mW cm-2. This research not only paves the way for new design paradigms in energy-related nanomaterials but also offers invaluable insights for the application and optimization of 2D-2D heterostructures in advanced electrochemical devices.

Multifunctional ytterbium oxide buffer for perovskite solar cells.

Perovskite solar cells (PSCs) comprise a solid perovskite absorber sandwiched between several layers of different charge-selective materials, ensuring unidirectional current flow and high voltage output of the devices1,2. A 'buffer material' between the electron-selective layer and the metal electrode in p-type/intrinsic/n-type (p-i-n) PSCs (also known as inverted PSCs) enables electrons to flow from the electron-selective layer to the electrode3-5. Furthermore, it acts as a barrier inhibiting the inter-diffusion of harmful species into or degradation products out of the perovskite absorber6-8. Thus far, evaporable organic molecules9,10 and atomic-layer-deposited metal oxides11,12 have been successful, but each has specific imperfections. Here we report a chemically stable and multifunctional buffer material, ytterbium oxide (YbOx), for p-i-n PSCs by scalable thermal evaporation deposition. We used this YbOx buffer in the p-i-n PSCs with a narrow-bandgap perovskite absorber, yielding a certified power conversion efficiency of more than 25%. We also demonstrate the broad applicability of YbOx in enabling highly efficient PSCs from various types of perovskite absorber layer, delivering state-of-the-art efficiencies of 20.1% for the wide-bandgap perovskite absorber and 22.1% for the mid-bandgap perovskite absorber, respectively. Moreover, when subjected to ISOS-L-3 accelerated ageing, encapsulated devices with YbOx exhibit markedly enhanced device stability.

Contextualizing the revised Patient Perception of Patient-Centeredness (PPPC-R) scale in primary healthcare settings: a validity and reliability evaluation study.

BACKGROUND: An English version of the Patient Perception of Patient-Centeredness (PPPC) scale was recently revised, and it is necessary to test this instrument in different primary care populations. AIM: This study aimed to assess the validity and reliability of a Chinese version of the PPPC scale. DESIGN: A mixed method was used in this study. The Delphi method was used to collect qualitative and quantitative data to address the content validity of the PPPC scale by calculating the Content Validity Index, Content Validity Ratio, the adjusted Kappa, and the Item Impact Score. Confirmatory factor analysis (CFA) and exploratory factor analysis (EFA) were used to assess the construct validity of the PPPC scale through a cross-sectional survey. The internal consistency was also assessed. SETTING/PARTICIPANTS: In the Delphi consultation, seven experts were consulted through a questionnaire sent by email. The cross-sectional survey interviewed 188 outpatients in Guangzhou city and 108 outpatients in Hohhot City from community health service centers or stations face-to-face. RESULTS: The 21 items in the scale were relevant to their component. The Item-level Content Validity Index for each item was higher than 0.79, and the average Scale-level content validity index was 0.97 in each evaluation round. The initial proposed 4-factor CFA model did not fit adequately. Still, we found a 3-factor solution based on our EFA model and the validation via the CFA model (model fit: [Formula: see text], P < 0.001, RMSEA = 0.044, CFI = 0.981; factor loadings: 0.553 to 0.888). Cronbach's α also indicated good internal consistency reliability: The overall Cronbach's α was 0.922, and the Cronbach's α for each factor was 0.851, 0.872, and 0.717, respectively. CONCLUSIONS: The Chinese version of the PPPC scale provides a valuable tool for evaluating patient-centered medical service quality.

Characterization of the pheromone receptors in Mythimna loreyi reveals the differentiation of sex pheromone recognition in Mythimna species.

Pheromone receptors (PRs) are key proteins in the molecular mechanism of pheromone recognition, and exploring the functional differentiation of PRs between closely related species helps to understand the evolution of moth mating systems. Pheromone components of the agricultural pest Mythimna loreyi have turned into (Z)-9-tetradecen-1-yl acetate (Z9-14:OAc), (Z)-7-dodecen-1-yl acetate (Z7-12:OAc), and (Z)-11-hexadecen-1-yl acetate, while the composition differs from that of M. separata in the genus Mythimna. To understand the molecular mechanism of pheromone recognition, we sequenced and analyzed antennal transcriptomes to identify 62 odorant receptor (OR) genes. The expression levels of all putative ORs were analyzed using differentially expressed gene analysis. Six candidate PRs were quantified and functionally characterized in the Xenopus oocytes system. MlorPR6 and MlorPR3 were determined to be the receptors of major and minor components Z9-14:OAc and Z7-12:OAc. MlorPR1 and female antennae (FA)-biased MlorPR5 both possessed the ability to detect pheromones of sympatric species, including (Z,E)-9,12-tetradecadien-1-ol, (Z)-9-tetradecen-1-ol, and (Z)-9-tetradecenal. Based on the comparison of PR functions between M. loreyi and M. separata, we analyzed the differentiation of pheromone recognition mechanisms during the evolution of the mating systems of 2 Mythimna species.

Cyanobacterial VOCs ß-ionone and ß-cyclocitral poisoning Lemna turionifera by triggering programmed cell death.

ß-Ionone and ß-cyclocitral are two typical components in cyanobacterial volatiles, which can poison aquatic plants and even cause death. To reveal the toxic mechanisms of the two compounds on aquatic plants through programmed cell death (PCD), the photosynthetic capacities, caspase-3-like activity, DNA fragmentation and ladders, as well as expression of the genes associated with PCD in Lemna turionifera were investigated in exposure to ß-ionone (0.2 mM) and ß-cyclocitral (0.4 mM) at lethal concentration. With prolonging the treatment time, L. turionifera fronds gradually died, and photosynthetic capacities gradually reduced and even disappeared at the 96th h. This demonstrated that the death process might be a PCD rather than a necrosis, due to the gradual loss of physiological activities. When L. turionifera underwent the death, caspase-3-like was activated after 3 h, and reached to the strongest activity at the 24th h. TUNEL-positive nuclei were detected after 12 h, and appeared in large numbers at the 48th h. The DNA was cleaved by Ca2+-dependent endonucleases and showed obviously ladders. In addition, the expression of 5 genes (TSPO, ERN1, CTSB, CYC, and ATR) positively related with PCD initiation was up-regulated, while the expression of 2 genes (RRM2 and TUBA) negatively related with PCD initiation was down-regulated. Therefore, ß-ionone and ß-cyclocitral can poison L. turionifera by adjusting related gene expression to trigger PCD.

Identification of algicidal monoterpenoids from four chemotypes of Cinnamomum camphora and their algicidal mechanisms on Microcystis aeruginosa.

Cyanobacterial blooms cause serious environmental issues, and plant secondary metabolites are considered as new algaecide for controlling them. Cinnamomum camphora produces a wide spectrum of terpenoids and has 4 main chemotypes, including linalool, camphor, eucalyptol and borneol chemotype. To develop the new cyanobacterial algaecide by using suitable chemotype of Cinnamomum camphora and the main terpenoids, we analyzed the terpenoid composition in the 4 chemotype extracts, evaluated the algicidal effects of the extracts and their typical monoterpenoids on Microcystis aeruginosa, and investigated the algicidal mechanism of the stronger algicidal agents. Among the 4 chemotypes, eucalyptol and borneol chemotype extracts exhibited stronger algicidal effects. In the 4 chemotype extracts, monoterpenoids were the main compounds, of which linalool, camphor, eucalyptol and borneol were the typical components. Among the 4 typical monoterpenoids, eucalyptol and borneol showed stronger algicidal effects, which killed 78.8% and 100% M. aeruginosa cells, respectively, at 1.2 mM after 48 h. In 1.2 mM eucalyptol and borneol treatments, the reactive oxygen species levels markedly increased, and the caspase-3-like activity also raised. With prolonging the treatment time, M. aeruginosa cells gradually shrank and wrinkled, and the cell TUNEL fluorescence intensity and DNA degradation gradually enhanced, indicating that the lethal mechanism is causing apoptosis-like programmed cell death (PCD). Therefore, eucalyptol and borneol chemotype extracts and their typical monoterpenoids have the potential for developing as algaecides to control cyanobacteria through triggering apoptosis-like PCD.

Buried-Metal-Grid Electrodes for Efficient Parallel-Connected Perovskite Solar Cells.

The limited conductivity of existing transparent conducting oxide (TCO) greatly restricts the further performance improvement of perovskite solar cells (PSCs), especially for large-area devices. Herein, buried-metal-grid tin-doped indium oxide (BMG ITO) electrodes are developed to minimize the power loss caused by the undesirable high sheet resistance of TCOs. By burying 140-nm-thick metal grids into ITO using a photolithography technique, the sheet resistance of ITO is reduced from 15.0 to 2.7 Ω sq-1 . The metal step of BMG over ITO has a huge impact on the charge carrier transport in PSCs. The PSCs using BMG ITO with a low metal step deliver power conversion efficiencies (PCEs) significantly better than that of their counterparts with higher metal steps. Moreover, compared with the pristine ITO-based PSCs, the BMG ITO-based PSCs show a smaller PCE decrease when scaling up the active area of devices. The parallel-connected large-area PSCs with an active area of 102.8 mm2 reach a PCE of 22.5%. The BMG ITO electrodes are also compatible with the fabrication of inverted-structure PSCs and organic solar cells. The work demonstrates the great efficacy of improving the conductivity of TCO by BMG and opens up a promising avenue for constructing highly efficient large-area PSCs.

B-N/B-O Contained Heterocycles as Fusion Locker in Multi-Resonance Frameworks towards Highly-efficient and Stable Ultra-Narrowband Emission.

Fusing condensed aromatics into multi-resonance (MR) frameworks has been an exquisite strategy to modulate the optoelectronic properties, which, however, always sacrifices the small full width at half maxima (FWHM). Herein, we strategically embed B-N/B-O contained heterocycles as fusion locker into classical MR prototypes, which could enlarge the π-extension and alleviate the steric repulsion for an enhanced planar skeleton to suppress the high-frequency stretching/ scissoring vibrations for ultra-narrowband emissions. Sky-blue emitters with extremely small FWHMs of 17-18 nm are thereafter obtained for the targeted emitters, decreased by (1.4-1.9)-fold compared with the prototypes. Benefiting from their high photoluminescence quantum yields of >90 % and fast radiative decay rates of >108  s-1 , one of those emitters shows a high maximum external quantum efficiency of 31.9 % in sensitized devices, which remains 25.8 % at a practical luminance of 1,000 cd m-2 with a small FWHM of merely 19 nm. Notably a long operation half-lifetime of 1,278 h is also recorded for the same device, representing one of the longest lifetimes among sky-blue devices based on MR emitters.

The association of personality traits with childhood obesity: A systematic review and meta-analysis.

BACKGROUND: A growing body of evidence has revealed an association between personality traits and obesity, but the findings regarding this association among children remain mixed. The aim of this review was to systematically summarize the literature regarding the associations between personality traits and childhood obesity. METHODS: The study has been registered on PROSPERO (CRD42022306529). We searched a total of 8 databases up to July 1, 2023, to identify both published studies and grey literature written in English. Personality traits were classified into five dimensions based on the widely used Five-Factor Model. We conducted random effects meta-analyses to quantitatively synthesize the data. Newcastle-Ottawa Scale was used to assess the quality of included studies. RESULTS: A total of 7 studies were included. The pooled correlation coefficient of 2 studies was -0.09 (95 % CI: -0.17 to 0.00; I2 = 0 %) and the pooled standardized mean difference of 3 studies was -0.08 (95 % CI: -0.13 to -0.03; I2 = 66 %), indicating that conscientiousness was negatively associated with childhood obesity. No consistent patterns were found in the associations between the other 4 dimensions of personality traits and BMI/obesity in children. LIMITATIONS: Our findings should be interpreted with caution due to the exclusion of non-English studies, the limited generalizability to Eastern population, and the scarcity body of evidence for present topic. CONCLUSIONS: Low conscientiousness has been found to be consistently associated with childhood obesity. Causal associations of personality traits with the risk of childhood obesity remain to be clarified in future studies.

Hippo-YAP/TAZ signaling in osteogenesis and macrophage polarization: Therapeutic implications in bone defect repair.

Bone defects caused by diseases or surgery are a common clinical problem. Researchers are devoted to finding biological mechanisms that accelerate bone defect repair, which is a complex and continuous process controlled by many factors. As members of transcriptional costimulatory molecules, Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) play an important regulatory role in osteogenesis, and they affect cell function by regulating the expression of osteogenic genes in osteogenesis-related cells. Macrophages are an important group of cells whose function is regulated by YAP/TAZ. Currently, the relationship between YAP/TAZ and macrophage polarization has attracted increasing attention. In bone tissue, YAP/TAZ can realize diverse osteogenic regulation by mediating macrophage polarization. Macrophages polarize into M1 and M2 phenotypes under different stimuli. M1 macrophages dominate the inflammatory response by releasing a number of inflammatory mediators in the early phase of bone defect repair, while massive aggregation of M2 macrophages is beneficial for inflammation resolution and tissue repair, as they secrete many anti-inflammatory and osteogenesis-related cytokines. The mechanism of YAP/TAZ-mediated macrophage polarization during osteogenesis warrants further study and it is likely to be a promising strategy for bone defect repair. In this article, we review the effect of Hippo-YAP/TAZ signaling and macrophage polarization on bone defect repair, and highlight the regulation of macrophage polarization by YAP/TAZ.

Characterization of a S1PR2 specific 11C-labeled radiotracer in streptozotocin-induced diabetic murine model.

BACKGROUND: Diabetes mellitus is a chronic progressive metabolic disorder that affects millions of people worldwide. Emerging evidence suggests the important roles of sphingolipid metabolism in diabetes. In particular, sphingosine-1-phosphate (S1P) and S1P receptor 2 (S1PR2) have important metabolic functions and are involved in several metabolic diseases. In diabetes, S1PR2 can effectively preserve ß cells and improve glucose/insulin tolerance in high-fat diet induced and streptozotocin (STZ)-induced diabetic mouse models. We previously developed a group of potent and selective S1PR2 ligands and radioligands. METHODS: In this study, we continued our efforts and characterized our leading S1PR2 radioligand, [11C]TZ34125, in a STZ-induced diabetic mouse model. [11C]TZ34125 was radiosynthesized in an automated synthesis module and in vitro saturation binding assay was performed using recombinant human S1PR2 membrane. In vitro saturation autoradiography analysis was also performed to determine the binding affinity of [11C]TZ34125 against mouse tissues. Type-1 diabetic mouse model was developed following a single high dose of STZ in C57BL/6 mice. Ex vivo biodistribution was performed to evaluate the distribution and amount of [11C]TZ34125 in tissues. In vitro autoradiography analysis was performed to compare the uptake of [11C]TZ34125 between diabetic and control animals in mouse spleen and pancreas. RESULTS: Our in vitro saturation binding assay using [11C]TZ34125 confirmed [11C]TZ34125 is a potent radioligand to recombinant human S1PR2 membrane with a Kd value of 0.9 nM. Saturation autoradiographic analysis showed [11C]TZ34125 has a Kd of 67.5, 45.9, and 25.0 nM to mouse kidney, spleen, and liver tissues respectively. Biodistribution study in STZ-induced diabetic mice showed the uptake of [11C]TZ34125 was significantly elevated in the spleen (~2 fold higher) and pancreas (~1.4 fold higher) compared to normal controls. The increased uptake of [11C]TZ34125 was further confirmed using autoradiographic analysis in the spleen and pancreases of STZ-induced diabetic mice, indicating S1PR2 can potentially act as a biomarker of diabetes in pancreases and inflammation in spleen. Future mechanistic analysis and in vivo quantitative assessment using non-invasive PET imaging in large animal model of diabetes is worthwhile. CONCLUSIONS: Overall, our data showed an increased uptake of our lead S1PR2-specific radioligand, [11C]TZ34125, in the spleen and pancreases of STZ-induced diabetic mice, and demonstrated [11C]TZ34125 has a great potential for preclinical and clinical usage for assessment of S1PR2 in diabetes and inflammation.

Flavonoid production in tomato mediates both direct and indirect plant defences against whiteflies in tritrophic interactions.

BACKGROUND: The role of plant flavonoids in direct defences against chewing and sap-sucking herbivorous insects has been extensively characterized. However, little is known about flavonoid-mediated tritrophic interactions between plants, herbivorous insects and natural enemies. In this study, we investigated how flavonoids modulate plant-insect interactions in a tritrophic system involving near-isogenic lines (NILs) of cultivated tomato (Solanum lycopersicum) with high (line NIL-purple hypocotyl [PH]) and low (line NIL-green hypocotyl [GH]) flavonoid levels, with a generalist herbivore whitefly (Bemisia tabaci) and its predatory bug (Orius sauteri). RESULTS: By contrasting levels of tomato flavonoids (direct defence) while manipulating the presence of predators (indirect defence), we found that high production of flavonoids in tomato was associated with a higher inducibility of direct defences and a stronger plant resistance to whitefly infestation and stimulated the emissions of induced volatile organic compounds, thereby increasing the attractiveness of B. tabaci-infested plants to the predator O. sauteri. Furthermore, suppression of B. tabaci population growth and enhancement of plant growth were mediated directly by the high production of flavonoids and indirectly by the attraction of O. sauteri, and the combined effects were larger than each effect individually. CONCLUSION: Our results show that high flavonoid production in tomato enhances herbivore-induced direct and indirect defences to better defend against herbivores in tritrophic interactions. Thus, the development of transgenic plants may present an opportunity to utilize the beneficial role of flavonoids in integrated pest management, while simultaneously maintaining or improving resistance against other pests and pathogens. © 2023 Society of Chemical Industry.

Low-dose lipopolysaccharide inducing continuous and obvious increase in urinary protein in hyperglycemic rats and the underlying mechanism.

Proteinuria is an important hallmark of diabetic nephropathy models, however it takes a long time for the proteinuria and is not stable. Therefore, low-dose lipopolysaccharide (LPS) was investigated in this work to induce rapid and stable proteinuria in hyperglycemic rats and the underlying mechanism was studied. Hyperglycemia rats was induced by high-fat feeding combined with intraperitoneal injection of streptozotocin (STZ). After 21 days, the model rats received a subinjury dose of 0.8 mg / kg LPS intraperitoneally (i.p.). We detected related biochemical indexes at different time periods after LPS injection and examined the expression of glomerular podocyte-associated proteins. Simultaneously, we measured expression of inflammatory factors, apoptotic proteins and albumin (ALB) in the renal cortex and renal medulla, respectively. PAS (Periodic Acid Schiff) staining was used to observe renal pathology. After LPS injection, urinary microalbumin (umALB) increased significantly and lasted longer. The expression of Nephrin, Podocin and necroptosis factor kappa B (NF-κB) in rennal cortex and Interleukin 18 (IL-18), Caspase-1, NF-κB and ALB in the renal medulla was significantly changed. Pathologically, the glomerular basement membrane was observed to be significantly thickened, the renal tubules were dilated, and the epithelial cells fell off in a circle. LPS promoted the continuous increase in urinary microalbumin in hyperglycemic rats, which was related to the damage to the glomerular basement membrane and renal tubular epithelial cells and to the inflammatory reaction in the kidney involved in NF-κB signaling, and this pathological damage can help to establish a stable model of diabetic nephropathy with increased proteinuria.

The PIWI-specific insertion module helps load longer piRNAs for translational activation essential for male fertility.

PIWI-clade proteins harness piRNAs of 24-33 nt in length. Of great puzzles are how PIWI-clade proteins incorporate piRNAs of different sizes and whether the size matters to PIWI/piRNA function. Here we report that a PIWI-Ins module unique in PIWI-clade proteins helps define the length of piRNAs. Deletion of PIWI-Ins in Miwi shifts MIWI to load with shorter piRNAs and causes spermiogenic failure in mice, demonstrating the functional importance of this regulatory module. Mechanistically, we show that longer piRNAs provide additional complementarity to target mRNAs, thereby enhancing the assembly of the MIWI/eIF3f/HuR super-complex for translational activation. Importantly, we identify a c.1108C>T (p.R370W) mutation of HIWI (human PIWIL1) in infertile men and demonstrate in Miwi knock-in mice that this genetic mutation impairs male fertility by altering the property of PIWI-Ins in selecting longer piRNAs. These findings reveal a critical role of PIWI-Ins-ensured longer piRNAs in fine-tuning MIWI/piRNA targeting capacity, proven essential for spermatid development and male fertility.

Chromosome-level genome assembly of the spotted alfalfa aphid Therioaphis trifolii.

The spotted alfalfa aphid (SAA, Therioaphis trifolii) (Hemiptera: Aphididae) is a destructive pest of cultivated alfalfa (Medicago sativa L.) that leads to large financial losses in the livestock industry around the world. Here, we present a chromosome-scale genome assembly of T. trifolii, the first genome assembly for the aphid subfamily Calaphidinae. Using PacBio long-read sequencing, Illumina sequencing, and Hi-C scaffolding techniques, a 541.26 Mb genome was generated, with 90.01% of the assembly anchored into eight scaffolds, and the contig and scaffold N50 are 2.54 Mb and 44.77 Mb, respectively. BUSCO assessment showed a completeness score of 96.6%. A total of 13,684 protein-coding genes were predicted. The high-quality genome assembly of T. trifolii not only provides a genomic resource for the more complete analysis of aphid evolution, but also provides insights into the ecological adaptation and insecticide resistance of T. trifolii.