Non-coding RNA Generated following Lariat Debranching Mediates Targeting of AID to DNA.

Transcription through immunoglobulin switch (S) regions is essential for class switch recombination (CSR), but no molecular function of the transcripts has been described. Likewise, recruitment of activation-induced cytidine deaminase (AID) to S regions is critical for CSR; however, the underlying mechanism has not been fully elucidated. Here, we demonstrate that intronic switch RNA acts in trans to target AID to S region DNA. AID binds directly to switch RNA through G-quadruplexes formed by the RNA molecules. Disruption of this interaction by mutation of a key residue in the putative RNA-binding domain of AID impairs recruitment of AID to S region DNA, thereby abolishing CSR. Additionally, inhibition of RNA lariat processing leads to loss of AID localization to S regions and compromises CSR; both defects can be rescued by exogenous expression of switch transcripts in a sequence-specific manner. These studies uncover an RNA-mediated mechanism of targeting AID to DNA.

Response of occurrence in microplastics and its adsorped cadmium capacity to simulated agricultural environmental scenarios in sludge-amended soil.

Large amounts of microplastics (MPs) enter the soil along with the amendment of sludge to soil. However, it is still unclear about the response of MPs occurrence and the adsorption behaviors of cadmium (Cd)on MPs to typical agricultural environmental scenarios. In present work, three kinds of MPs (polyethylene, polypropylene, and polystyrene) were chosen to investigate that response in three agricultural environmental scenarios with sludge-amended soil, including dry-wet alteration (7 d, five cycles), microbial addition (Bacillus subtilis, 0.05 g/g soil), and Ultraviolet (UV) irradiation (340 nm, 4 × 15 W, 4 d). The results showed that there was the highest adsorption capacity of Cd on MPs (36.21, 45.15, 12.43 µg/g for PE, PP, PS, respectively) after UV irradiation exceeding those from MPs triggered by other two scenarios). UV irradiation caused an increase in the abundance of Streptomyces, an expansion in specific surface area, a significant change in surface morphologies, an improvement in crystallinity or the formation of new crystals, and an enhancement in C-O and CO content, and then resulted in the incremental adsorption capacity of Cd on MPs. The findings are important of significance for controlling the environmental risks from sludge MPs via carrying heavy metals in the soil-plant systems.

St13 protects against disordered acinar cell arachidonic acid pathway in chronic pancreatitis.

BACKGROUND: Early diagnosis and treatment of chronic pancreatitis (CP) are limited. In this study, St13, a co-chaperone protein, was investigated whether it constituted a novel regulatory target in CP. Meanwhile, we evaluated the value of micro-PET/CT in the early diagnosis of CP. METHODS: Data from healthy control individuals and patients with alcoholic CP (ACP) or non-ACP (nACP) were analysed. PRSS1 transgenic mice (PRSS1Tg) were treated with ethanol or caerulein to mimic the development of ACP or nACP, respectively. Pancreatic lipid metabolite profiling was performed in human and PRSS1Tg model mice. The potential functions of St13 were investigated by crossing PRSS1Tg mice with St13-/- mice via immunoprecipitation and lipid metabolomics. Micro-PET/CT was performed to evaluate pancreatic morphology and fibrosis in CP model. RESULTS: The arachidonic acid (AA) pathway ranked the most commonly dysregulated lipid pathway in ACP and nACP in human and mice. Knockout of St13 exacerbated fatty replacement and fibrosis in CP model. Sdf2l1 was identified as a binding partner of St13 as it stabilizes the IRE1α-XBP1s signalling pathway, which regulates COX-2, an important component in AA metabolism. Micro-PET/CT with 68Ga-FAPI-04 was useful for evaluating pancreatic morphology and fibrosis in CP model mice 2 weeks after modelling. CONCLUSION: St13 is functionally activated in acinar cells and protects against the cellular characteristics of CP by binding Sdf2l1, regulating AA pathway. 68Ga-FAPI-04 PET/CT may be a very valuable approach for the early diagnosis of CP. These findings thus provide novel insights into both diagnosis and treatment of CP.

Influence of sludge treatment methods on behaviors of microplastics adsorbed cadmium and its driving factors.

The complicated contamination of microplastics (MPs) and heavy metals in sludge has garnered substantial attention in recent years; however, research on the behavior of MPs loading of heavy metals in sludge after sludge treatment methods is limited. Four representative sludge treatment methods were selected herein: anaerobic digestion, thermal drying, thermal hydrolysis (TH), and aerobic composting. Before and after sludge treatment, the chemical bonding of MPs, cadmium (Cd) adsorption properties, and metabolic changes in the microbial community succession was analyzed, and the factors influencing differences in Cd sorption by sludge MPs were explored. The results revealed that Cd adsorption by MPs occurs as multilayer physical adsorption that can be well fitted by Freundlich isotherms. Compared with the other three treatments, TH led to the most significant effect on the chemical bonding properties of the MPs, with a more than two-fold increase in C-O single bonds and CO double bonds, as well as adsorption of the highest amount of Cd at 767 µg/g. In addition, sludge conductivity and water content also affected Cd sorption capacity, with correlation coefficients of 0.405 and -0.384. Pedobacter, Flavobacterium, Lysobacter, and Sphingobacterium in the sludge presented a high degree of coupling with adsorption capacity, it was inferred that the above dominant species of bacteria may affect the adsorption of Cd by microplastics through the production of extracellular enzyme forms.

Progress on genic male sterility gene in soybean.

Male sterility refers to the phenomenon that stamens cannot grow normally and produce viable pollen grains in plants. Hybrid seed production by taking advantage of the trait of male sterility is an effective and quick strategy to increase crop yield. Up to date, the yield of rice (Oryza sativa L.), maize (Zea mays L.), wheat (Triticum aestivum L.) and other crops has been greatly increased based on hybrid vigor utilization. Soybean (Glycine max (L.) Merr.) is a self-pollination species, artificial emasculation is not only time-consuming, but also labor-intensive and economically impracticable. So far, large scale hybrid breeding has not been performed in soybean due to the shortage of male sterile lines suitable for hybrid production. Therefore, it is urgent to identify a stable male sterile system for the rapid utilization of heterosis in soybean. In this review, we summarize the progress on the discovery of soybean genic male sterility (GMS) mutants and GMS genes. Combining with the investigation of GMS genes in Arabidopsis, rice and maize, we provide important insights into the identification and potential utilization of GMS genes in soybean in the perspective of reverse genetics.

Plasmonic behaviors of metallic AZO thin film and AZO nanodisk array.

Aluminum-doped zinc oxide (AZO) is well known as transparent conducting material for electro-optical devices, but is rarely used as plasmonic material, particularly on the localized surface plasmon resonance (LSPR) behavior of AZO nanostructure and its plasmonic devices. In this study, we systematically investigate the plasmonic behaviors of AZO thin films and patterned AZO nanostructures with various structural dimensions under different annealing treatments. We find that AZO film can possess highly-tunable, metal-like, and low-loss plasmonic property and the LSPR characteristic of AZO nanostructure is observed in the near-infrared (NIR) region under proper annealing conditions. Finally, environmental index sensing is performed to demonstrate the capability of AZO nanostructure for optical sensing application. High index sensitivity of 873 nm per refractive index unit (RIU) variation is obtained in experiment.

Syntheses of Platinum-Sulindac Complexes and Their Nanoparticles as Targeted Anticancer Drugs.

Platinum(II)-sulindac complexes [{η2 -C5 H4 SN(O)}Pt(DMSO){O(C=O)Sulindac}], [{η2 -C5 H4 SN(O)}PtCl{(S=O)Sulindac}], [{η2 -C5 H4 SN(O)}PtCl{(S=O)Sulindac-succinimide}], and [{η2 -C5 H4 SN(O)}PtCl{(S=O)Sulindac-thymidine}] were synthesized that exhibited IC50 values of 2.9-4.8 µm against human oral cancer cells OECM1. The poly(lactic-co-glycolic acid) (PLGA) encapsulated [{η2 -C5 H4 SN(O)}PtCl{(S=O)Sulindac}] also showed cytotoxic activity although less potent than the pristine species.

Graphene oxide as the passivation layer for Cu(x)O photocatalyst on a plasmonic Au film and the corresponding photoluminescence study.

The contribution of graphene oxide (GO) on photocatalytic effects of Cu(x)O on plasmonic Au is investigated. It is found that the H(2) evolution rate from pure water is enhanced 1.4 fold using the visible-active Cu(x)O/GO photocatalyst, as compared with Cu(x)O without GO. In addition, the intensity of photoluminescence of Cu(x)O/GO can be enhanced as much as 2.85 fold as compared with Cu(x)O without GO. The enhancement is due to the negative fixed charge in GO, which can passivate the surface of Cu(x)O and suppress recombination of minority electrons at the surface. The results from optical characterization in this study can help to prove the proposed mechanism of passivation.

Inter-allelic prion propagation reveals conformational relationships among a multitude of [PSI] strains.

Immense diversity of prion strains is observed, but its underlying mechanism is less clear. Three [PSI] prion strains--named VH, VK, and VL--were previously isolated in the wild-type yeast genetic background. Here we report the generation and characterization of eight new [PSI] isolates, obtained by propagating the wild-type strains with Sup35 proteins containing single amino-acid alterations. The VH strain splits into two distinct strains when propagated in each of the three genetic backgrounds, harboring respectively single mutations of N21L, R28P, and Gi47 (i.e. insertion of a glycine residue at position 47) on the Sup35 N-terminal prion-forming segment. The six new strains exhibit complex inter-conversion patterns, and one of them continuously mutates into another. However, when they are introduced back into the wild-type background, all 6 strains revert to the VH strain. We obtain two more [PSI] isolates by propagating VK and VL with the Gi47 and N21L backgrounds, respectively. The two isolates do not transmit to other mutant backgrounds but revert to their parental strains in the wild-type background. Our data indicate that a large number of [PSI] strains can be built on three basic Sup35 amyloid structures. It is proposed that the three basic structures differ by chain folding topologies, and sub-strains with the same topology differ in distinct ways by local structural adjustments. This "large number of variations on a small number of basic themes" may also be operative in generating strain diversities in other prion elements. It thus suggests a possible general scheme to classify a multitude of prion strains.

The complete mitochondrial genome of Aphidius colemani (Hymenoptera: Braconidae: Aphidiinae).

The genome-level features are crucial genetic resources for species identification and phylogenetic analysis. Here, the complete mitochondrial genome of Aphidius colemani Viereck 1912 (Hymenoptera: Braconidae: Aphidiinae) was sequenced, determined and analyzed. The circular genome is 16,372 bp in length with an overall base composition of 38.9% for A, 46.2% for T, 6.7% for C, and 8.2% for G. The mitochondrial genome of A. colemani contained 13 protein-coding genes that initiated by the ATN codon, 22 transfer RNA genes, two ribosomal RNA genes (rRNAs), and a control region (CR). It shared the same gene arrangement patterns that occurred in two tRNA clusters of trnI-trnQ-trnM and trnW-trnC-trnY with Aphidius gifuensis. Phylogenetic analyses using Bayesian inference and Maximum-likelihood methods supported that the two species of Aphidiinae formed a clade and sister to other subfamilies of Braconidae.

Laryngopharyngeal reflux disease: Updated examination of mechanisms, pathophysiology, treatment, and association with gastroesophageal reflux disease.

Laryngopharyngeal reflux disease (LPRD) is an inflammatory condition in the laryngopharynx and upper aerodigestive tract mucosa caused by reflux of stomach contents beyond the esophagus. LPRD commonly presents with sym-ptoms such as hoarseness, cough, sore throat, a feeling of throat obstruction, excessive throat mucus. This complex condition is thought to involve both reflux and reflex mechanisms, but a clear understanding of its molecular mechanisms is still lacking. Currently, there is no standardized diagnosis or treatment protocol. Therapeutic strategies for LPRD mainly include lifestyle modifications, proton pump inhibitors and endoscopic surgery. This paper seeks to provide a comprehensive overview of the existing literature regarding the mechanisms, patho-physiology and treatment of LPRD. We also provide an in-depth exploration of the association between LPRD and gastroesophageal reflux disease.

Students' persistence intention in MOOCs in the psychomotor domain: An extended 3P model of the teaching and learning perspective.

This study proposed and tested a model adapted from Biggs' 3P model that quantifies the behaviors of students who completed MOOCs (Massive Open Online Courses) in order to design intervention measures for low retention rates. Psychomotor domain data from 300 MOOC learners was analyzed in a covariance-based structural equation model (CB-SEM) to analyze the direct and indirect effects of various factors. Results show the basic psychological needs theory (BPNT) in the presage stage significantly positively correlated with engagement in the process stage. Meanwhile, the process stage exhibited a significantly positive correlation with the product stage, representing persistence intention (PI). Furthermore, a full mediation effect was observed among the presage, process, and product stages. The mediating effect demonstrates that higher student engagement leads to more positive exertion on BNPT and PI to complete the course. Moreover, results show bolstering students' behavioral, emotional, and cognitive engagement strengthens their PIs.

Self-Assembled Monolayer for Low-Power-Consumption, Long-Term-Stability, and High-Efficiency Quantum Dot Light-Emitting Diodes.

Quantum dot light-emitting diodes (QLEDs) are an emerging class of optoelectronic devices with a wide range of applications. However, there still exist several drawbacks preventing their applications, including long-term stability, electron leakage, and large power consumption. To circumvent the difficulties, QLEDs based on a self-assembled hole transport layer (HTL) with reduced device complexity are proposed and demonstrated. The self-assembled HTL is prepared from poly[3-(6-carboxyhexyl)thiophene-2,5-diyl] (P3HT-COOH) solution in N,N-dimethylformamide (DMF) forming a well-ordered monolayer on an indium-tin-oxide (ITO) anode. The P3HT-COOH monolayer has a smaller HOMO band offset and a sufficiently large electron barrier with respect to the CdSe/ZnS quantum dot (QD) emission layer, and thus it is beneficial for hole injection into and electron leakage blocking from the QD layer. Interestingly, the QLEDs exhibit an excellent conversion efficiency (97%) in turning the injected electron-hole pairs into light emission. The performance of the resulting QLEDs possesses a low turn-on voltage of +1.2 V and a maximum external quantum efficiency of 25.19%, enabling low power consumption with high efficiency. Additionally, those QLEDs also exhibit excellent long-term stability without encapsulation with over 90% luminous intensity after 200 days and superior durability with over 70% luminous intensity after 2 h operation under the luminance of 1000 cd m-2. The outstanding device features of our proposed QLEDs, including low turn-on voltage, high efficiency, and long-term stability, can advance the development of QLEDs toward facile large-area mass production and cost-effectiveness.

Recent advances in the application of machine learning methods to improve identification of the microplastics in environment.

Environmental pollution by microplastics (MPs) is a significant and complex global issue. Existing MPs identification methods have demonstrated significant limitations such as low resolution, long imaging time, and limited particle size analysis. New and improved methods for MPs identification are topical research areas, with machine learning (ML) algorithms proven highly useful in recent years. Critical literature reviews on the latest developments in this area are limited. This study closes this gap and summarizes the progress made over the last 10 years in using ML algorithms for identifying and quantifying MPs. We identified diverse combinations of ML methods and fundamental techniques for MPs identification, such as Fourier-transform infrared spectroscopy, Raman spectroscopy, and near-infrared spectroscopy. The most widely used ML model is the support vector machine, which effectively improves the conventional analysis method for spectral quality defects and improves detection accuracy. Artificial neural network models exhibit improved recognition effects, with shorter detection times and better MPs recognition efficiency. Our review demonstrates the potential of ML in improving the identification and quantification of MPs.

Optically Encodable and Erasable Multilevel Nonvolatile Flexible Memory Device Based on Metal-Organic Frameworks.

Multilevel and flexible nonvolatile memory (NVM) is a promising candidate for data storage in next-generation devices but its high bias and low mobility of conducting channels are often its drawbacks. In this study, we demonstrate a low bias of smaller than 0.1 V and a high-mobility graphene layer as a conducting channel for flexible optoelectronic NVM based on a composite thin film of indium-based MOF-derived InCl3 and 4,4-oxydiphthalic anhydride (odpta), Na[In3(odpt)2(OH)2(H2O)2](H2O)4, and reduced graphene oxide (rGO). The optoelectronic NVM device can be encoded and erased optically by ultraviolet (UV) light and visible light, respectively. Our device also achieves memory states over 192 (6-bit storage) distinct levels, which can emerge as mass data storage. It also shows an excellent endurance of write-erase cycles under irradiation with a laser of varying wavelengths, the mechanical stability of more than 1000 bending cycles, and stable retention for longer than 10 000 s. These results open an alternative route for developing low bias and innovative optoelectronic technologies.

IL-7-Treated Periodontal Ligament Cells Regulate Local Immune Homeostasis by Modulating Treg/Th17 Cell Polarization.

Both interleukin (IL)-7 and human periodontal ligament cells (hPDLCs) have immunomodulatory properties. However, their combined effect on CD4+T cells has never been studied. In this study, we aimed to investigate the effect of conditioned medium of hPDLCs treated with rhIL-7 on the differentiation of CD4+T cells into regulatory T cells/T helper 17 cells (Treg/Th17 cells) and observe the effect of IL-7 on the immunomodulatory properties of PDLCs. After hPDLCs were treated with different concentrations of rhIL-7 for 24 h, the collected supernatants were used to incubate CD4+T cells for 3 days. A gamma-secretase inhibitor (DAPT) was used to suppress the activation of the Notch1 signaling pathway. Cell proliferation, apoptosis, and necrosis were determined using the cell counting kit-8 (CCK-8) and flow cytometry (FCM). The expressions of forkhead box P3 (Foxp3) in CD4+T cells and transforming growth factor (TGF-ß) and IL-6 in the supernatants were determined by ELISA. Reverse transcription-quantitative PCR (RT-qPCR), and the Western blot (WB) determined the mRNA levels and protein expression of various target factors. FCM was used to detect the mean fluorescence intensity of PD-L1 in hPDLCs and to analyze the differentiation of Treg/Th17 cells. Our results showed that IL-7 promoted proliferation and inhibited apoptosis in hPDLCs, promoted the expression of TGF-ß, PD-L1, Notch1, Jagged1, and Hes1, and inhibited the levels of hypoxia-inducible factor (HIF)-1α and TCF7, whereas the addition of DAPT effectively reversed these effects. Importantly, we found that the conditioned medium of hPDLCs treated with rhIL-7 promoted the polarization of CD4+T cells into Treg cells but had no significant effect on the differentiation of Th17 cells. Our study indicated that treatment of PDLCs with IL-7 can promote the polarization of CD4+T cells into Treg cells by modulating the expression of inflammatory factors and signaling molecules through activating the Notch1 signaling pathway, thus participating in the regulation of immune homeostasis in the periodontal microenvironment.

Strain-specific sequences required for yeast [PSI+] prion propagation.

Amyloid polymorphism underlies the prion strain phenomenon where a single protein polypeptide adopts different chain-folding patterns to form self-propagating cross-beta structures. Three strains of the yeast prion [PSI], namely [VH], [VK], and [VL], have been previously characterized and are amyloid conformers of the yeast translation termination factor Sup35. Here we define specific sequences of the Sup35 protein that are necessary for in vivo propagation of each of these prion strains. By sequential substitution of residues 5-55 of Sup35 by proline and insertion of glycine at alternate sites in this segment, specific mutations have been identified that interfere selectively with the propagation of each of the three prion strains in yeast: the [VH] strain requires amino acid residues 7-21; [VK] requires residues 9-37; and [VL] requires residues 5 to at least 52. Minimal polypeptide segments capable of encoding prion conformations were defined by assembly of recombinant Sup35 fragments on purified prion nuclei to form amyloid fibers in vitro, whose infectivity was assayed in yeast. For the [VK] and [VL] strains, the minimal fragments approximately coincide with the strain-specific sequences defined by mutations of the N-terminal portion of the intact Sup35 (1-685); and for the [VH] strain, a longer Sup (1-53) fragment is required. Polymorphic structures of other amyloids might similarly involve different stretches of polypeptides to form cross-beta amyloid cores with distinct molecular recognition surfaces.

Rational Design, Pharmacomodulation, and Synthesis of [68Ga]Ga-Alb-FAPtp-01, a Selective Tumor-Associated Fibroblast Activation Protein Tracer for PET Imaging of Glioma.

Dynamic changes in the tumor-associated fibroblast activation protein (FAP) expression in tumors of different stages may be helpful for prognostic evaluation and treatment response monitoring, making this protein a promising surveillance biomarker for timely diagnosis of malignant tumors and effective planning of patient care. To prospectively verify the diagnostic efficacy value of the developed FAP tracers, [68Ga]Ga-FAPtp and [68Ga]Ga-Alb-FAPtp-01, dynamic/static positron emission tomography (PET)/computed tomography scans were acquired for tumor-targeting studies in vivo and in comparison with the well-established clinically used tracer [68Ga]Ga-FAPI-04. The optimized rationally designed FAP-targeting PET tracer, [68Ga]Ga-Alb-FAPtp-01, with albumin-binding capability demonstrated prominent tumor uptake over time. The mean standard uptake value (SUV) and the tumor/muscle (T/M) ratio were as high as 1.775 ± 0.179 SUV and T/M = 5.9, 1.533 ± 0.222 SUV and T/M = 6.7, and 1.425 ± 0.204 SUV and T/M = 9.5, respectively, at 1, 2, and 3 h. Its improved tumor uptake and pharmacokinetics suggest that the [68Ga]Ga-Alb-FAPtp-01 tracer can noninvasively detect FAP activation in vivo, permitting a precise definition of its roles in tumors of different stages and yielding insights regarding FAP-targeted radiotherapeutic strategies at the molecular level.

[Research status of bioweathering control of stone buildings]. / çŸ³è´¨å»ºç­‘çš„ç”Ÿç‰©é£ŽåŒ–é˜²æ²»ç ”ç©¶çŽ°çŠ¶.

Stone buildings exposed to natural environment inevitably subject to various factors. Among which, biodeterioration caused by bacteria, fungi, algae, lichen, and moss is widespread. The long-term cumulative effect of biodeterioration will lead to irreversible changes in the aesthetic characteristics, physical and chemical properties of stone buildings. Therefore, it is necessary to control the biodeterioration of stone buildings. Here, we summarized four traditional methods including heat shock treatments, laser and ultraviolet radiation, application of biocides, and presented typical examples. We analyzed several emerging techniques, such as synergistic effect of physical and chemical methods, plant extracts and nanomaterials biocides, and reviewed their advantages, disadvantages as well as applicability. Aiming to provide a reference for the research of biodeterioration prevention and conservation of stone buildings, we discussed the preventive methods for biodeterioration of stone building and the assessment methods to test the effects of such methods, and prospected the future research direction.

The interaction between acute oligomer Abeta(1-40) and stress severely impaired spatial learning and memory.

In this study, we investigated whether stress can enhance the toxicity of oligomer Abeta(1-40) in the mouse brain. Stress was applied to the animals, consisting of a 2-day inescapable foot shock followed by 3-weekly situation reminders (SRs). We found that stress significantly affected not only the amygdala-dependent (anxiety) but also the hippocampal-dependent (spatial learning and memory) behaviors through the oxidative damage caused in these two regions. However, oligomer Abeta(1-40) treatment alone did not induce behavioral impairment. In addition, combined oligomer Abeta(1-40) and stress treatment increased the glucocorticoid receptor (GR)/mineralocorticoid receptor (MR) ratio and the expression of corticotrophin releasing factor 1 (CRF-1) receptor in the hippocampus. Changes in the components of the hypothalamic-pituitary-adrenal (HPA) axis, such as the GR/MR ratio and CRF-1 level, were observed, accompanied by increasing Abeta accumulation, oxidative stress, nuclear transcription factor (NF-kappaB) hypoactivity, and apoptotic signaling in the hippocampus, and decreasing calbindin D28K and NMDA receptor 2A/2B (NR2A/2B) in the hippocampus, along with alteration of the cholinergic neurons (ChAT) in the medium septum/diagnoid band (MS/DB), noradrenergic neurons (TH) in the locus coeruleus (LC), and serotonergic neurons (5-HT) in the Raphe nucleus. Therefore, apoptosis and synaptic dysfunction in the hippocampus severely induced the impairment of spatial learning and memory. These results suggest that stress may play an important role in the early stages of Alzheimer's disease (AD), and an antioxidant strategy might be a potential therapeutic approach for stress-mediated disorders.