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Alzheimer’s disease is characterized by two major neuropathological hallmarks—the extracellular β-amyloid plaques and intracellular neurofibrillary tangles consisting of aggregated and hyperphosphorylated Tau protein. Recent studies suggest that dysregulation of the microtubule-associated protein Tau, especially specific proteolysis, could be a driving force for Alzheimer’s disease neurodegeneration. Tau physiologically promotes the assembly and stabilization of microtubules, whereas specific truncated fragments are sufficient to induce abnormal hyperphosphorylation and aggregate into toxic oligomers, resulting in them gaining prion-like characteristics. In addition, Tau truncations cause extensive impairments to neural and glial cell functions and animal cognition and behavior in a fragment-dependent manner. This review summarizes over 60 proteolytic cleavage sites and their corresponding truncated fragments, investigates the role of specific truncations in physiological and pathological states of Alzheimer’s disease, and summarizes the latest applications of strategies targeting Tau fragments in the diagnosis and treatment of Alzheimer’s disease.

Abstract Background Alamandine is a newly characterized peptide of renin angiotensin system. Our study aims to investigate the osteo-preservative effects of alamandine, explore underlying mechanism and bring a potential preventive strategy for postmenopausal osteoporosis in the future. Methods An ovariectomy (OVX)-induced rat osteoporosis model was established for in vivo experiments. Micro-computed tomography and three-point bending test were used to evaluate bone strength. Histological femur slices were processed for immunohistochemistry (IHC). Bone turnover markers and nitric oxide (NO) concentrations in serum were determined with enzyme-linked immunosorbent assay (ELISA). The mouse embryo osteoblast precursor (MC3T3-E1) cells were used for in vitro experiments. The cell viability was analysed with a Cell Counting Kit‑8. We performed Alizarin Red S staining and alkaline phosphatase (ALP) activity assay to observe the differentiation status of osteoblasts. Western blotting was adopted to detect the expression of osteogenesis related proteins and AMP-activated protein kinase/endothelial nitric oxide synthase (AMPK/eNOS) in osteoblasts. DAF-FM diacetate was used for semi-quantitation of intracellular NO. Results In OVX rats, alamandine alleviated osteoporosis and maintained bone strength. The IHC showed alamandine increased osteocalcin and collagen type I α1 (COL1A1) expression. The ELISA revealed alamandine decreased bone turnover markers and restored NO level in serum. In MC3T3-E1 cells, alamandine promoted osteogenic differentiation. Western blotting demonstrated that alamandine upregulated the expression of osteopontin, Runt-related transcription factor 2 and COL1A1. The intracellular NO was also raised by alamandine. Additionally, the activation of AMPK/eNOS axis mediated the effects of alamandine on MC3T3-E1 cells and bone tissue. PD123319 and dorsomorphin could repress the regulating effect of alamandine on bone metabolism. Conclusion Alamandine attenuates ovariectomy-induced osteoporosis by promoting osteogenic differentiation via AMPK/eNOS axis.

The loreyi leafworm Mythimna loreyi (Lepidoptera: Noctuidae) is a serious pest of agriculture that causes particular damage to Gramineae crops in Asia, Europe, Australia, Africa, and the Middle East. Low temperature is one of the important environmental factors that limits the survival, distribution, colonization, and abundance of M. loreyi. However, the metabolic synthesis pathways of cold-tolerant substances in M. loreyi and the key genes involved in the regulation under cold stress remain largely unknown. In this study, we sequenced the transcriptomes of three developmental stages (larvae, pupae, and adults) of M. loreyi to discover the molecular mechanisms of their responses to cold stress. In total, sequencing generated 120.64 GB of clean data from 18 samples, of which 19,459 genes and 1740 differentially expressed genes (DEGs) were identified. The enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that many DEGs were mainly enriched in pathways associated with energy metabolism and hormone metabolism. Among these, genes encoding multiple metabolic enzymes, cuticle proteins (CPs), and heat shock proteins (HSPs) were differentially expressed. These results indicate that there are significant differences among the three developmental stages of M. loreyi exposed to cold stress and provide a basis for further studying the molecular mechanisms of cold tolerance in insects.

Holotrichia parallela is an important plant pest. Comparative feeding experiments showed that the egg production, oviposition duration and survival rate of H. parallela beetles were significantly higher when they fed on elm leaves than when they fed on willow or purpus privet leaves. RNA sequencing was used to determine transcriptomic changes associated with oviposition. Comparative transcriptome analysis revealed that the beetles that fed on elm and willow had a total of 171 genes with differential expression. When the beetles fed on elm and purpus privet, 3568 genes had differential expression. The vitellogenesis, ovarian serine protease, odorant-binding proteins, acyl-CoA synthetase and follicle cell proteins were commonly upregulated genes in elm-fed beetles compared with those fed on willow/purpus privet leaves. The involvement of the follicle cell protein 3C gene in the regulation of oviposition was confirmed using RNA interference. The results provide insights into the molecular mechanisms underlying oviposition in H. parallela feeding on different host plants. This study also describes a method for identifying potentially effective genes for pest control.

Abstract Fundamental understanding and control of the electronic structure evolution in rare‐earth nickelates is a fascinating and meaningful issue, as well as being helpful to understand the mechanism of recently discovered superconductivity. Here the dimensionality effect on the ground electronic state in high‐quality (NdNiO3) m/(SrTiO3)1 superlattices is systematically studied through transport and soft X‐ray absorption spectroscopy. The metal‐to‐insulator transition temperature decreases with the thickness of the NdNiO3 slab decreasing from bulk to 7 unit cells, then increases gradually as m further reduces to 1 unit cell. Spectral evidence demonstrates that the stabilization of insulating phase can be attributed to the increase of the charge‐transfer energy between O 2p and Ni 3d bands. The prominent multiplet feature on the Ni L3 edge develops with the decrease of NdNiO3 slab thickness, suggesting the strengthening of the charge disproportionate state under the dimensional confinement. This work provides convincing evidence that dimensionality is an effective knob to modulate the charge‐transfer energy and thus the collective ground state in nickelates.

Chemically-inducible gene expression systems are valuable tools for rational control of gene expression both for basic research and biotechnology. However, most chemical inducers are confined to certain groups of organisms. Therefore, dissecting interactions between different organisms could be challenging using existing chemically-inducible systems. We engineered a mandipropamid-induced gene expression system (Mandi-T7) based on evolved split T7 RNAP system. As a proof-of-principle, we induced GFP expression in E. coli cells grown inside plant tissue.

This article established the error model based on pixel parameters to predict the light intensity quantization error in pulse width modulation (PWM) image sensor, attributed to non-linear response, comparator delay and synchronous reading mechanism. The PWM image sensor encodes light intensity into time interval of consecutive pulses, makes the quantization process of light intensity exceptionally impact the accuracy of the imaging quality. Especially in large pixel array, the synchronous readout scheme introduces quantization error. A PWM image sensor with 400(H) $\times $ 250(V) pixel array was tested to evaluate the model, and the measurements show that the pixel parameters affect the fluctuation of quantization error. With 300lux illuminance and $25\mu \text{s}$ reading period, the smallest error fluctuation range (11%–15%) can be obtained. The proposed model can suppress the fluctuation of the quantization error in PWM image sensor and help to achieve improved performance of image quality.

Abstract Background Alzheimer’s disease (AD) is a progressive neuro-degenerative disease with a major manifestation of dementia. MicroRNAs were reported to regulate the transcript expression in patients with Alzheimer’s disease (AD). In this study, we investigated the roles of miR-138, a brain-enriched miRNA, in the AD cell model. Methods The targets of miRNA-138 was predicted by bioinformatic analysis. The expression levels of DEK at both mRNA and protein levels were determined by qRT-PCR and Western blot, respectively. Luciferase assays were carried out to examine cell viabilities. Hoechst 33258 staining was used to detect cell apoptosis. Results Our results demonstrated that the expression levels of miR-138 were increased in AD model, and DEK was a target of miR-138. Overexpression of miR-138 in SH-SY5Y cells obviously down-regulated the expression of DEK in SH-SY5Y cells, resulting in the inactivation of AKT and increased expression levels of proapoptotic caspase-3. MiR-138 mediated-suppression of DEK increased the susceptibility of cell apoptosis. Conclusions MicroRNA-138 promotes cell apoptosis of SH-SY5Y by targeting DEK in SH-SY5Y AD cell model. The regulation of miR-138 may contribute to AD via down-regulation of the DEK/AKT pathway.

Aging is associated with immune attrition that may impact the effectiveness of the immune system to protect the host from pathogens. Here the authors show that immune aging is associated with alterations in the Wnt/β-catenin signaling and reduced stem cell memory T lymphocytes, hinting the Wnt/β-catenin pathway as a potential therapy target.

Colorectal cancer (CRC) has become the second leading cause of new cancer cases and the fifth of cancer deaths in China, and early detection is the most effective way to reduce the incidence and mortality of CRC. A number of methylated DNA biomarkers have been found to associate with CRC and precancerous lesions in stool samples, indicating stool methylated DNA biomarkers are potential tools for CRC early detection. In this study, approximately 5 g of stool specimen was collected from 230 subjects (124 in the training set and 106 in the validation set). Stool DNA was extracted and bisulfite-converted, followed by ColoDefense test, a multiplex qPCR assay, that simultaneously detects methylated SEPT9 (mSEPT9) and methylated SDC2 (mSDC2). Youden index was employed to determine the cut-off value of ColoDefense test for stool specimens. In the training set, the optimized cut-off value of stool ColoDefense test was: mSEPT9 analyzed with 3/3 algorithm and mean mSEPT9 Ct values of

Gastric cancer (GC) is fifth most frequently diagnosed cancer and second leading cause of cancer in China. More than 80% of GC are diagnosed at an advanced stage due to low uptake rate of invasive screening method. The performance of methylated SFRP2 test was evaluated in 236 plasma samples, including 92 patients with GC, 16 intestinal metaplasia patients, 26 gastric fundic gland polyp patients, 13 small adenoma patients, 39 hyperplastic polyp patients, and 50 control patients. The sensitivity of plasma methylated SFRP2 was compared to serum CEA, CA72-4, CA19-9, and CA242 results in 79 patients with GC. The sensitivities for detecting GC and gastric intestinal metaplasia by methylated SFRP2 test were 60.9% and 56.3% with a specificity of 86.0%. Methylated SFRP2 test had significantly higher positive detection rate for patients with GC than gastric fundic gland polyp, small adenoma, and hyperplastic polyp patients. In 79 patients with GC, the sensitivities of CEA, CA72-4, CA19-9, and CA242 for detecting GC were 22.8%, 16.5%, 12.7%, and 11.4%. In comparison, the sensitivity of methylated SFRP2 test for detecting GC was 58.2%. Plasma methylated SFRP2 test may become a valuable tool for the noninvasive detection of GC and precursor lesions and showed higher sensitivity than serum tumor markers.

Colorectal cancer (CRC) is the most common type of malignancies of the gastrointestinal tract worldwide. Plasma methylated SEPT9 test has been used clinically for CRC screening for several years, but the study about the performance comparison between plasma and stool has rarely been reported. In this study, 124 plasma samples, 100 stool samples, and 60 sets of plasma and paired stool samples were collected and tested by a methylated SEPT9 test in three PCR replicates. The results indicated methylated SEPT9 levels in stool samples were significant higher than those in plasma samples (p < 0.0001). When a plasma sample was called positive if 1 out of 3 PCR replicates was positive and a stool sample was called positive if 3 out of 3 PCR replicates were positive with a mean Cp value of less than 40.0, stool methylated SEPT9 test achieved similar sensitivity (83.3% vs 85.6%) and specificity (92.1% vs 90.1%) to those by plasma methylated SEPT9 test, and the overall concordance rate is 78.3%. However, stool methylated SEPT9 test showed 35.9 and 7.9% improvement in detecting advanced adenomas (AA) and stage I–II CRC in comparison to plasma methylated SEPT9 test. The AUC for plasma methylated SEPT9 and stool methylated SEPT9 in detecting CRC were 0.885 (95% CI: 0.832–0.938) and 0.935 (95% CI: 0.895–0.975), respectively. In conclusion, stool methylated SEPT9 test showed higher sensitivities for detection AA and early stage CRC compared with plasma methylated SEPT9 test, and stool methylated SEPT9 test may be a more suitable tool for early stage CRC screening.

The compressive deformation behaviors of 410 martensitic stainless steel were investigated on a Gleeble-1500 thermomechanical simulator, and the experimental stress–strain data were obtained. The measured flow stress was corrected for friction and temperature. A constitutive equation that accounts for the influence of strain was established, and the hot-processing maps at different strain were plotted. The microstructure evolution of the hot-deformation process was studied on the basis of microstructural observations at high temperatures. Phase-transformation experiments on 410 steel were conducted at high temperatures to elucidate the effects of temperature on the delta-ferrite content. The initial forging temperature and optimum process parameters were obtained on the basis of the processing map and the changes in the delta-ferrite content at high temperatures.

Neurofibrillary tangles (NFTs) made up of hyperphosphorylated tau are a histopathological hallmark of Alzheimer’s disease (AD) and related tauopathies. Hyperphosphorylation of tau is responsible for its loss of normal physiological function, gain of toxicity and its aggregation to form NFTs. Injection of misfolded tau seeds into mouse brain induces tau aggregation, but the nature of tau phosphorylation in pathologic tau seeded pathology is unclear. In the present study, we injected hyperphosphorylated and oligomeric tau isolated from AD brain (AD P-tau) into hippocampus of human tau transgenic mice and found that in addition to tau aggregation/pathology, tau was hyperphosphorylated at Ser202/Thr205, Thr212, Ser214, Thr217, Ser262, and Ser422 in AD P-tau injected hippocampus and at Ser422 in the contralateral hippocampus and in the ipsilateral cortex. AD P-tau-induced AD-like high molecular weight aggregation of tau that was SDS- and reducing agent-resistant and site-specifically hyperphosphorylated in the ipsilateral hippocampus. There were no detectable alterations in levels of tau phosphatases or tau kinases in AD P-tau-injected brains. Furthermore, we found that hyperphosphorylated tau was easier to be captured by AD P-tau and that aggregated tau was more difficult to be dephosphorylated than the non-aggregated tau by protein phosphatase 2A (PP2A). Based on these findings, we speculate that AD P-tau seeds hyperphosphorylated tau to form aggregates, which resist to the dephosphorylation by PP2A, resulting in hyperphosphorylation and pathology of tau.

The 2015 Nobel Prize in Physiology or Medicine has been awarded to avermectins and artemisinin, respectively. Avermectins produced by Streptomyces avermitilis are excellent anthelmintic and potential antibiotic agents. Because wild-type strains only produce low levels of avermectins, much research effort has focused on improvements in avermectin production to meet the ever increasing demand for such compounds. This review describes the strategies that have been widely employed and the future prospects of synthetic biology applications in avermectin yield improvement. With the help of genome sequencing of S. avermitilis and an understanding of the avermectin biosynthetic/regulatory pathways, synthetic and systems biotechnology approaches have been applied for precision engineering. We focus on the design and synthesis of biological chassis, parts, devices, and modules from diverse microbes to reconstruct and optimize their dynamic processes, as well as predict favorable effective overproduction of avermectins by a 4Ms strategy (Mine, Model, Manipulation, and Measurement).

The scarab beetle, Anomala corpulenta Motschulsky (Coleoptera: Scarabaeoidea), is a widespread and destructive pest in China. Vision is one of the most important means of acquiring information about the external environment. In order to contribute to the understanding of the perception of visual stimuli in this species, the light sensitivity and spectral responses of the scarab beetle, A. corpulenta, were measured by using an electroretinogram (ERG) technique. In total, 14 monochromatic light intensities, between 340 and 605 nm, were applied to the compound eyes of A. corpulenta under varying levels of adaptation to dark and light conditions. The results showed that all light stimuli induced an ERG response, with varied amplitudes. The spectral sensitivity curve of dark-adapted eyes showed one major peak (~400 nm; near-ultraviolet), a secondary peak (from 498 to 562 nm; yellow-green) and the third peakat 460 nm. By contrast, in light-adapted eyes, only a near-UV peak was observed. From these results, we conclude that the compound eye of A. corpulenta is likely to have at least three spectral types of photoreceptor. Significance of differences were also recorded in the responses of male and female compound eyes, as well as diurnally and nocturnally. The amplitude of ERG in response to white-light stimuli varied with the light intensity: The stronger the luminance, the higher the ERG value. This suggests that the compound eye of A. corpulenta adapts quickly to changing light conditions, enabling A. corpulenta to maintain nocturnal activities.

The guava fruit fly, Bactrocera correcta, is one of the major pests affecting mango (Mangifera indica) and guava (Psidium guajava) production in China. The compound β-caryophyllene was identified from the rectal gland extracts of wild B. correcta males and was demonstrated to be a more specific and potent male lure than methyl eugenol (ME) for B. correcta. In order to find potential additional pheromone attractants for the monitoring and mass-trapping of this fruit fly, a series of chemical and behavioral assays were conducted in this study. Ten compounds were identified from the rectal glands of virgin B. correcta females. These compounds consisted of five major compounds (i.e., ethyl dodecanoate, ethyl tetradecanoate, ethyl (E)-9-hexadecenoate, ethyl hexadecanoate, and ethyl (Z)-9-octadecenoate) in high quantities, and other compounds (i.e., octanal, N-(3-methylbutyl) acetamide, (Z)-9-tricosene, ethyl octadecanoate, and ethyl eicosanoate) in trace amounts, while virtually no compounds were found in male rectal glands. The bioassays indicate that female rectal gland extracts are attractive to virgin females and males. Furthermore, a cyclical production of the five major compounds was found, recurring at roughly 10-d intervals with peaks in 10–13-, 25-, and 35-d-old females. Collectively, these results will contribute to the understanding of pheromone communication in B. correcta and may provide important information for improving existing monitoring and control methods for this pest.

Fall armyworm, Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae), is a target species of transgenic corn (Zea mays L.) that expresses single and pyramided Bacillus thuringiensis (Bt) toxin. In 2014, S. frugiperda were collected from a light trap in North Carolina, and a total of 212 F1/F2 isofemale lines of S. frugiperda were screened for resistance to Bt and non-Bt corn. All of the 212 isolines were susceptible to corn tissue expressing Cry1A.105 + Cry2Ab, Cry1F + Cry1A.105 + Cry2Ab, and Cry1F + Cry1Ab + Vip3Aa20. Growth rate bioassays were performed to isolate non-recessive Bt resistance alleles. Seven individuals out of the 212 isofemale lines carried major non-recessive alleles conferring resistance to Cry1F. A pooled colony was created from the seven individuals. This colony was 151.21 times more resistant to Cry1F than a known-susceptible population and was also resistant to Cry1A.105, but was not resistant to Cry2Ab and Vip3Aa20. The results demonstrate that field populations of S. frugiperda collected from North Carolina are generally susceptible to Cry1F, but that some individuals carry resistant alleles. The data generated in this study can be used as baseline data for resistance monitoring.

BACKGROUND: Many insects enter a developmental arrest (diapause) that allows them to survive harsh seasonal conditions. Despite the well-established ecological significance of diapause, the molecular basis of this crucial adaptation remains largely unresolved. Sitodiplosis mosellana (Gehin), the orange wheat blossom midge (OWBM), causes serious damage to wheat throughout the northern hemisphere, and sporadic outbreaks occur in the world. Traits related to diapause appear to be important factors contributing to their rapid spread and outbreak. To better understand the diapause mechanisms of OWBM, we sequenced the transcriptome and determined the gene expression profile of this species. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we performed de novo transcriptome analysis using short-read sequencing technology (Illumina) and gene expression analysis with a tag-based digital gene expression (DGE) system. The sequencing results generated 89,117 contigs, and 45,713 unigenes. These unigenes were annotated by Blastx alignment against the NCBI non-redundant (nr), Clusters of orthologous groups (COG), gene orthology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. 20,802 unigenes (45.5% of the total) matched with protein in the NCBI nr database. Two digital gene expression (DGE) libraries were constructed to determine differences in gene expression profiles during diapause and non-diapause developmental stages. Genes related to diapause were analyzed in detail and in addition, nine diapause-related genes were analyzed by real time PCR. CONCLUSIONS/SIGNIFICANCE: The OWBM transcriptome greatly improves our genetic understanding and provides a platform for functional genomics research of this species. The DGE profiling data provides comprehensive information at the transcriptional level that facilitates our understanding of the molecular mechanisms of various physiological aspects including development and diapause stages in OWBM. From this study it is evident that various genes coding metabolic enzymes are crucial for diapause and metamorphosis.

The wheat midge, Sitodiplosis mosellana, is an important pest in Northern China. We tested the hypothesis that the population structure of this species arises during a range expansion over the past 30 years. This study used microsatellite and mitochondrial loci to conduct population genetic analysis of S. mosellana across its distribution range in China. We found strong genetic structure among the 16 studied populations, including two genetically distinct groups (the eastern and western groups), broadly consistent with the geography and habitat fragmentation. These results underline the importance of natural barriers in impeding dispersal and gene flow of S. mosellana populations. Low to moderate genetic diversity among the populations and moderate genetic differentiation (F ST = 0.117) between the two groups were also found. The populations in the western group had lower genetic diversity, higher genetic differentiation and lower gene flow (F ST = 0.116, Nm = 1.89) than those in the eastern group (F ST = 0.049, Nm = 4.91). Genetic distance between populations was positively and significantly correlated with geographic distance (r = 0.56, P

Abstract Background Human bocavirus 2(HBoV2) and other human bocavirus species (HBoV, HBoV3, and HBoV4) have been discovered recently. But the precise phylogenetic relationships among these viruses are not clear yet. Methods We collected 632 diarrhea and 162 healthy children in Lanzhou, China. Using PCR, Human bocavirus (HBoV), HBoV2, HBoV3 and HBoV4 were screened. The partial genes of NS, NP1 and VP, and two nearly complete sequences of HBoV2 were obtained. Result Phylogenetic analysis showed the different genes of HBoV2 strain were homogenous with different reference strains. HBoV3 may be a recombinant derived from HBoV and HBoV4. We also observed that the VP1 and VP2 region of HBoV3 is as similar to HBoV2 as to HBoV4. Conclusions A single genetic lineage of HBoV2 is circulating in children with and without gastroenteritis in Lanzhou, China. Current evidence in this study was not enough to support recombination between HBoV2 strains, and HBoV3 may be a recombinant between HBoV and the common ancestor of HBoV2 and HBoV4.