AdipoRon Ameliorates Synaptic Dysfunction and Inhibits tau Hyperphosphorylation through the AdipoR/AMPK/mTOR Pathway in T2DM Mice.

There is growing evidence showing that adiponectin (APN) can improve Alzheimer's disease(AD)-like pathological changes by improving insulin resistance. However, the role of AdipoRon (an Adiponectin receptor agonist) on synaptic plasticity and cognitive dysfunction in the early stages of type 2 diabetes mellitus(T2DM) remains unknown. In this study, we investigated the neuroprotective effect and the molecular mechanism underlying the effect of AdipoRon in T2DM mice. We found that AdipoRon significantly restored the cognitive deficits in T2DM mice, including shorter escape latency, more crossing times, increased distances, and percentage of time in the target quadrant. In addition, AdipoRon treatment up-regulated synaptic proteins (PSD95, SYN, GAP43, and SYP), increased the number of hippocampal synapses and attenuated synaptic damage, including the length, the number and the density of dendritic spines in CA1 and DG regions. Furthermore, AdipoRon attenuated Tau phosphorylation at multiple AD-related sites (p-tau 205, p-tau 396, p-tau 404) by promoting AdipoR expression and activating the AMPK/mTOR pathway. Our data suggests that AdipoRon exerts neuroprotective effects on the T2DM mice, which may be mediated by the activation of the AdipoR/AMPK/mTOR signaling pathway.

Bimetallic Gold/Silver and Bioactive Camptothecin Hybrid Nanoparticles for Eradication of Cancer Stem Cells in a Combination Manner.

The defeat of cancer is still a challenge due to the existence of cancer stem cells (CSCs) because they resist conventional chemotherapy via multifactor regulated mechanisms. Consequently, one-dimensional action toward CSCs cannot work. Herein, we used rationally designed hybrid nanoparticles as a combined cancer therapy, hoping to form a multidimensional control network. In this paper, gold/silver alloy nanoparticle decorated camptothecin nanocrystals were formulated according to complementary anti-CSC mechanisms from gold, silver, and organic drug. This smart drug formulation could combine chemotherapy and thermotherapy, target different tumor sites, and demonstrate versatile toxicity profiles from each component. Major results indicated that this nanosystem demonstrated indiscriminately effective cytotoxic/proapoptotic/necrotic activity against bulk MCF-7 cells and their CSC subpopulation, in particular under laser ablation. Moreover, this nanosystem displayed enhanced antineoplastic activity against CSC spheroids, resulting in a significant reduction in their number and size, that is, their self-renewal capacity. All the results indicated that CSCs upon treatment of these new hybrid nanoparticles underwent reduced stemness and conversion from the original quiescent state and recovered their sensitivity toward chemotherapy. The relevant anticancer mechanism was ascribed to NIR-pH dual responsive drug release, synergistic/combined thermo-chemotherapy of organic drug and inorganic alloy nanoparticles, enhanced cellular uptake mediated by alloy nanoparticles, and Ag+-induced biomembrane damage. This thermo-chemotherapy platform provides a new combinatorial strategy for inorganic and organic agents in the complete elimination of CSCs.

The Microbiomes in Lichen and Moss Biocrust Contribute Differently to Carbon and Nitrogen Cycles in Arid Ecosystems.

Biological soil crusts (biocrusts) are distributed in arid and semiarid regions across the globe. Microorganisms are an essential component in biocrusts. They add and accelerate critical biochemical processes. However, little is known about the functional genes and metabolic processes of microbiomes in lichen and moss biocrust. This study used shotgun metagenomic sequencing to compare the microbiomes of lichen-dominated and moss-dominated biocrust and reveal the microbial genes and metabolic pathways involved in carbon and nitrogen cycling. The results showed that Actinobacteria, Bacteroidetes, and Acidobacteria were more abundant in moss biocrust than lichen biocrust, while Proteobacteria and Cyanobacteria were more abundant in lichen biocrust than moss biocrust. The relative abundance of carbohydrate-active enzymes and enzymes associated with carbon and nitrogen metabolism differed significantly between microbiomes of the two biocrust types. However, in the microbial communities of both biocrust types, respiration pathways dominated over carbon fixation pathways. The genes encoding carbon monoxide dehydrogenase were more abundant than those encoding ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCo) involved in carbon fixation. Similarly, metabolic N-pathway diversity was dominated by nitrogen reduction, followed by denitrification, with nitrogen fixation the lowest proportion. Gene diversity involved in N cycling differed between the microbiomes of the two biocrust types. Assimilatory nitrate reduction genes had higher relative abundance in lichen biocrust, whereas dissimilatory nitrate reduction genes had higher relative abundance in moss biocrust. As dissolved organic carbon and soil organic carbon are considered the main drivers of the community structure in the microbiome of biocrust, these results indicate that biocrust type has a pivotal role in microbial diversity and related biogeochemical cycling.

Octalithium, Tetrasodium, and Decalithium Compounds Based on Pyrrolyl Ligands: Synthesis, Structures, and Activation of the C-H Bonds of Pyrrolyl Rings and C═N Bonds of a Series of Ligands by Organolithium Reagents.

The organometallic compounds of lithium ions have garnered continuous interest as indispensable precursors for the syntheses of organometallic complexes of main-group metals, transition metals, lanthanide metals, and actinide metals. In this work, we present a strategy for the preparation of a series of polynuclear lithium complexes. This methodology features the utilization of organolithium reagents both as metal sources to coordinate with the ligands and as nucleophilic reagents to undergo nucleophilic addition to the C═N bonds of the ligands. Reaction of a ligand HL1 [HL1 = 2-(((1-(2-(dimethylamino)ethyl)-1H-pyrrol-2-yl)methylene)amino)phenol] with n-BuLi produced complex [Li8(L1a)4]·1.5Tol (1·1.5Tol) [H2L1a = 2-((1-(1-(2-(dimethylamino)ethyl)-1H-pyrrol-2-yl)pentyl)amino)phenol]. One prominent feature regarding the formation of 1·1.5Tol is the occurrence of nucleophilic addition of n-BuLi to the C═N bond of HL1, leading to the generation of a new [L1a]2- ligand that contains both aminophenol and 1-(2-pyrrolyl)alkylamine scaffolds. The developed protocol can be adapted to a series of organolithium reagents. Compounds [Li8(L1b)4] (2) and [Li8(L1c)4] (3) were afforded by treatment of HL1 with sec-BuLi and LiCH2SiMe3, respectively. Reaction of an analogous ligand HL2 [HL2 = 2-(((1-(2-(dimethylamino)ethyl)-1H-pyrrol-2-yl)methylene)amino)-4-methylphenol] with n-BuLi generated compound [Li8(L2a)4] (4). C═N bond activation was not observed in the reaction of HL1 with NaOtBu, and the complex [Na4(L1)4]·Tol (5·Tol) was obtained. A decanuclear complex [Li10(L3a)2(L3b)2] (6) was also prepared via the reaction of HL3 [HL3 = 2-(2-((((1H-pyrrol-2-yl)methylene)amino)methyl)-1H-pyrrol-1-yl)-N,N-dimethylethan-1-amine] with t-BuLi. A remarkable feature in terms of the synthesis of 6 is the simultaneous occurrence of hydrogen atom abstraction from the C-H bond of the pyrrolyl ring and nucleophilic addition to the C═N bond of the HL3 ligand by t-BuLi. A series of amines containing biologically and physiologically important moieties were achieved by hydrolysis of the crude products from the reactions of the HL1-HL3 ligands and organolithium reagents. This work provides an efficient approach to high-nuclearity lithium compounds as well as a series of amines.

Electromagnetic Radiation Exposure and Childhood Leukemia: Meta-Analysis and Systematic Review.

Objective: Leukemia is the most prevalent cancer among children and adolescents. This study investigated the potential association between exposure to magnetic fields and the risk of pediatric leukemia. Methods: We conducted a comprehensive search of electronic databases, including Scopus, EMBASE, Cochrane, Web of Science, and Medline, up to December 15, 2022, to identify relevant studies examining the link between childhood leukemia and magnetic field exposure. Results: The first meta-analysis revealed a statistically significant inverse association between pediatric leukemia and magnetic field strengths ranging from 0.4 µT to 0.2 µT, suggesting a reduced risk associated with this range. The second meta-analysis focused on wiring configuration codes and observed a potential link between residential magnetic field exposure and childhood leukemia. Pooled relative risk estimates were 1.52 (95% CI = 1.05-2.04, P = .021) and 1.58 (95% CI = 1.15-2.23, P = .006) for exposure to 24-hour magnetic field measurements, suggesting a possible causal relationship. In the third meta-analysis, the odds ratios for the exposure groups of 0.1 to 0.2 µT, 0.2 to 0.3 µT, 0.3 to 0.4 µT, and 0.4 µT above 0.2 µT were 1.09 (95% confidence interval = 0.82 to 1.43 µT), 1.14 (95% confidence interval = 0.68 to 1.92 µT), and 1.45 (95% confidence interval = 0.87 to 2.37 µT), respectively. In contrast to the findings of the three meta-analyses, there was no evidence of a statistically significant connection between exposure to 0.2 µT and the risk of juvenile leukemia. A further result showed no discernible difference between the two groups of children who lived less than 100 meters from the source of magnetic fields and those who lived closer (OR = 1.33; 95% CI = 0.98-1.73 µT). Conclusions: The collective results of three meta-analyses, encompassing magnetic field strengths ranging from 0.1 µT to 2.38 µT, underscore a statistically significant association between the intensity of magnetic fields and the occurrence of childhood leukemia. However, one specific analysis concluded that no apparent relationship exists between exposure to 0.1 µT and an elevated risk of leukemia development in children.

First report of Fusarium meridionale causing Fusarium head blight of wheat in Henan Province, China.

Fusarium graminearum and F. asiaticum have been found as a major cause of Fusarium head blight (FHB) of wheat (Triticum aestivum L.), especially in Henan Province of China (Zhang et al. 2014; Xu et al. 2021). In May 2021, a survey to determine the composition of Fusarium species infecting wheat heads was conducted in commercial fields in Henan. A total of 395 diseased spikes with premature whitening symptom were collected from 31 commercial fields in Henan. Symptomatic spikelets were excised, surface-sterilized for 10 s in 70% ethanol followed by 1 min in 3% sodium hypochlorite, rinsed three times with autoclaved distilled water, and then plated onto potato dextrose agar (PDA) medium. Isolated colonies that resembled Fusarium species were transferred to fresh PDA plates and purified using a single spore method. Species were identified based on sequence analysis of the translation elongation factor-1α (TEF) and trichothecene 3-Oacetyltransferase (Tri 101) gene (Proctor et al. 2009). The results indicated that F. graminearum (43.3%), F. asiaticum (47.8%), F. pseudograminearum (6.6%) were the main causal agents of FHB in Henan. However, nine isolates (2.3%) were found to be identical to F. meridionale by sequence comparison in GenBank, and eight isolates of which came from three fields with 1% to 2% diseased spikes near Reservoir Luhun (34.1255° N, 112.1111° E, altitude: 388 m above sea level), Songxian County of Henan. The isolates of F. meridionale were transferred onto carnation leaf agar (CLA) and incubated at 20℃ under black light blue illumination. Macroconidia were abundant, relatively slender, curved to almost straight, commonly six- to seven-septate, and 27.0 to 61.0 (average 44.0) µm × 3.2 to 6.8 (average 5.3) µm. Microconidia were not observed. The TEF sequences (Accession nos. OM460748 to OM460756) and the Tri 101 sequences (OM460759 to OM460767) of the nine isolates showed 99 to 100% similarity with the TEF and Tri 101 sequences of F. meridionale NRRL 28436 and NRRL 28723 (AF212435 and AF212436 (TEF); AF212582 and AF212683 (Tri 101)). To complete Koch's postulates, the pathogenicity of the fungus was tested by using the single floret inoculation method by injecting 20-µl conidial suspension (5 × 105 conidia per milliliter) into healthy inflorescences of wheat cultivar Bainong 207 at anthesis in the field. Another 30 healthy inflorescences were injected with sterile distilled water. The heads were covered with polyethylene bags that were removed after 2 days. Twenty days after inoculation, while control inflorescences were asymptomatic, the F. meridionale-inoculated inflorescences showed 12% bleached spikelets per spike. By using the methodology described above, the fungus was re-isolated from infected spikelets of inoculated wheat heads but not from the controls. Although F. meridionale has frequently been reported in association with Fusarium ear rot (FER) of maize in Chongqing City and Gansu Province (Zhang et al. 2014; Zhou et al. 2018), and rice FER in Sichuan Province (Dong et al. 2020), to our knowledge, this is the first report of F. meridionale from diseased wheat heads in Henan, China. Further investigation is needed to gain a better understanding of this species by collecting isolates from different cropping system in Henan, which maize-wheat and rice-wheat rotation fields have coexisted in the region.

SRP54 mediates circadian rhythm-related, temperature-dependent gene expression in Drosophila.

Recent studies have shown that alternative splicing (AS) plays an important role in regulating circadian rhythm. However, it is not clear whether clock neuron-specific AS is circadian rhythm dependent and what genetic and environmental factors mediate the circadian control of AS. By genome-wide RNA sequencing, we identified SRP54 is one of the Clock (Clk) dependent alternative splicing factors. Genetic interaction between Clock and SRP54 alleles showed that the enhancement of the circadian phenotype increased with temperature, being strongest at 29 °C and weakest at 18 °C. The alternative splicing and differential gene expression profile of Clock and SRP54 overlapped with the circadian-related gene profiles identified in various genome-wide studies, indicating that SRP54 is involved in circadian rhythm. By analyzing of the RNA-seq results at different temperatures, we found the roles of Clock and SRP54 are temperature dependent. We also found multiple novel temperature-dependent transcripts not documented in current databases.

Neuronal Scaffold Protein ARMS Interacts with Synaptotagmin-4 C2AB through the Ankyrin Repeat Domain with an Unexpected Mode.

The ankyrin repeat-rich membrane spanning (ARMS), a transmembrane neuronal scaffold protein, plays a fundamental role in neuronal physiology, including neuronal development, polarity, differentiation, survival and angiogenesis, through interactions with diverse partners. Previous studies have shown that the ARMS negatively regulates brain-derived neurotrophic factor (BDNF) secretion by interacting with Synaptotagmin-4 (Syt4), thereby affecting neurogenesis and the development and function of the nervous system. However, the molecular mechanisms of the ARMS/Syt4 complex assembly remain unclear. Here, we confirmed that the ARMS directly interacts with Syt4 through its N-terminal ankyrin repeats 1-8. Unexpectedly, both the C2A and C2B domains of Syt4 are necessary for binding with the ARMS. We then combined the predicted complex structural models from AlphaFold2 with systematic biochemical analyses using point mutagenesis to underline the molecular basis of ARMS/Syt4 complex formation and to identify two conserved residues, E15 and W72, of the ARMS, as essential residues mediating the assembly of the complex. Furthermore, we showed that ARMS proteins are unable to interact with Syt1 or Syt3, indicating that the interaction between ARMS and Syt4 is specific. Taken together, the findings from this study provide biochemical details on the interaction between the ARMS and Syt4, thereby offering a biochemical basis for the further understanding of the potential mechanisms and functional implications of the ARMS/Syt4 complex formation, especially with regard to the modulation of BDNF secretion and associated neuropathies.

Candidate powdery mildew resistance gene in wheat landrace cultivar Hongyoumai discovered using SLAF and BSR-seq.

BACKGROUND: Wheat powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is an important disease affecting wheat production. Planting resistant cultivars is an effective, safe, and economical method to control the disease. Map construction using next-generation sequencing facilitates gene cloning based on genetic maps and high-throughput gene expression studies. In this study, specific-locus amplified fragment sequencing (SLAF) was used to analyze Huixianhong (female parent), Hongyoumai (male parent) and two bulks (50 homozygous resistant and 50 susceptible F2:3 segregating population derived from Huixianhong × Hongyoumai to determine a candidate gene region for resistance to powdery mildew on the long arm of chromosome 7B in wheat landrace Hongyoumai. Gene expressions of candidate regions were obtained using bulked segregant RNA-seq in 10 homozygous resistant and 10 susceptible progeny inoculated by Bgt.. Candidate genes were obtained using homology-based cloning in two parents. RESULTS: A 12.95 Mb long candidate region in chromosome 7BL was identified, and five blocks in SLAF matched the scaffold of the existing co-segregation marker Xmp1207. In the candidate region, 39 differentially expressed genes were identified using RNA-seq, including RGA4 (Wheat_Chr_Trans_newGene_16173)-a disease resistance protein whose expression was upregulated in the resistant pool at 16 h post inoculation with Bgt. Quantitative reverse transcription (qRT)-PCR was used to further verify the expression patterns in Wheat_Chr_Trans_newGene_16173 that were significantly different in the two parents Hongyoumai and Huixianhong. Two RGA4 genes were cloned based on the sequence of Wheat_Chr_Trans_newGene_16173, respectively from two parent and there was one amino acid mutation: S to G in Huixianhong on 510 loci. CONCLUSION: The combination of SLAF and BSR-seq methods identified a candidate region of pmHYM in the chromosome 7BL of wheat landrace cultivar Hongyoumai. Comparative analysis between the scaffold of co-segregating marker Xmp1207 and SLAF-seq showed five matching blocks. qRT-PCR showed that only the resistant gene Wheat_Chr_Trans_newGene_16173 was significantly upregulated in the resistant parent Hongyoumai after inoculation with Bgt, and gene cloning revealed a difference in one amino acid between the two parent genes, indicating it was involved in the resistance response and may be the candidate resistance gene pmHYM.

Measurement error model of the bio-inspired polarization imaging orientation sensor.

This article studies the measurement error model and calibration method of the bio-inspired polarization imaging orientation sensor (BPIOS), which has important engineering significance for promoting bio-inspired polarization navigation. Firstly, we systematically analyzed the measurement errors in the imaging process of polarized skylight and accurately established an error model of BPIOS based on Stokes vector. Secondly, using the simulated Rayleigh skylight as the incident surface light source, the influence of multi-source factors on the measurement accuracy of BPIOS is quantitatively given for the first time. These simulation results can guide the later calibration of BPIOS. We then proposed a calibration method of BPIOS based on geometric parameters and the Mueller matrix of the optical system and conducted an indoor calibration experiment. Experimental results show that the measurement accuracy of the calibrated BPIOS can reach 0.136°. Finally, the outdoor performance of BPIOS is studied. Outdoor dynamic performance test and field compensation were performed. Outdoor results show that the heading accuracy of BPIOS is 0.667°.

Design and collaborative optimization method of multilayer coatings to correct polarization aberration of optical systems.

Multilayer coatings induce a significant polarization aberration in optical systems with high numerical aperture (NA) and wide field of view, which will cause wavefront distortion and imaging degradation. Studies have used low-polarization coatings (LPC) design to reduce the coating-induced polarization aberration. However, the polarization aberration caused by LPC remain evident in systems with large incident angles and many coated surfaces. In this paper, a hybrid optimization algorithm (HOA) is proposed to enhance the design accuracy of LPC. Based on the HOA, a collaborative optimization method is developed to simultaneously design coatings with different polarization properties for multiple surfaces, which can correct polarization aberration by mutual compensation between the coated surfaces and other optical elements in a single system. Finally, a high NA lithographic lens is simulated as an example to verify the collaborative optimization method. The simulation demonstrates that this method is superior to conventional methods. This research provides a new way to correct the polarization aberration and is applicable to any systems coated with multilayer coatings.

Extra sex combs buffers sleep-related stresses through regulating Heat shock proteins.

The impact of global warming on the life of the earth is increasingly concerned. Previous studies indicated that temperature changes have a serious impact on insect sleep. Sleep is critical for animals as it has many important physiological functions. It is of great significance to study the regulation mechanism of temperature-induced sleep changes for understanding the impact of global warming on insects. More importantly, understanding how these pressures regulate sleep can provide insights into improving sleep. In this study, we found that extra sex combs (ESC) are a regulatory factor in this process. Our data showed that ESC was an upstream negative regulatory factor of Heat shock proteins (Hsps), and it could regulate sleep in mushroom and ellipsoid of Drosophila. ESC mutation exaggerates the sleep change caused by temperature, while buffering the shortening of life caused by sleep deprivation. These phenotypes can be rescued by Hsps mutants. Therefore, we concluded that the ESC buffers sleep-related stresses through regulating Hsps.

Mathematical modeling and experimental verification of aging human eyes polarization sensitivity.

The polarization perception sensitivity of the human eyes affects the perceived polarized image quality. In this paper, we used polarized spatiotemporal structured images to develop a spatiotemporal age mapping of the polarization perception of human eyes. We built an optical modulation transfer function mathematical model of the aging human eyes with spatiotemporal frequency domains and introduced the Stokes vector to analyze the polarized images. The proposed model provides a testing method based on a set of polarization images with spatiotemporal frequencies varying according to the perception of differently aged viewers. Then, we experimentally validated the proposed model by performing polarization perception tests on a group of volunteers. The test method has the diagnostic potential to confirm the health of human eyes and identify potential age-related macular diseases.

First report of Fusarium falciforme causing root rot of soybean (Glycine max L.) in Henan, China.

Soybean (Glycine max L.) is an important crop in China owing to its high oil and protein content, with approximately 9.88 million ha of production in 2020. In September 2021, soybean plants showing wilting, root necrosis, and brown discoloration were observed, with an average incidence of approximately 36% in seven fields in Yongcheng City and Shangqiu City, Henan, China. Fungi were isolated from small pieces of symptomatic root tissues after being surface-sterilized (70% ethanol for 50 s followed by 3% NaClO for 1.0 min), rinsed three times in sterile distilled water, and then placed on PDA and incubated at 25℃ for 5 days in the dark. Single-spore cultures of twenty isolates were obtained by dilution plating (Leslie and Summerell 2006), and then were cultured on carnation leaf agar at 25℃ for 14 days. Macroconidia were mostly 3-septate, hyaline, falcate, with slightly curved apexes, with well-developed foot cells and blunt apical cells, and measured 29.3 to 45.0 (average 34.7) µm × 4.6 to 8.0 (average 6.0) µm. Microconidia were one to two celled, hyaline, and measured 11.9 to 29.0 (average 20.1) µm × 3.9 to 7.6 (average 5.7) µm. These morphological characteristics were consistent with previous descriptions of the Fusarium solani species complex (FSSC) (Leslie and Summerell 2006; Summerell et al. 2003). Partial sequences of translation elongation factor-1α (TEF) and RNA polymerase II subunit (RPB2) gene were PCR amplified using region specific primers as described by O'Donnell et al. (2008). The nucleotide sequences obtained from twenty isolates were deposited in GenBank with accession numbers of ON375405-ON375423, ON697187 (TEF) and ON331917-ON331936 (RPB2). Phylogenetic analysis revealed the isolates were nested within F. falciforme based on the DNA sequences of the above two genes (Chitrampalam and Nelson 2016). Pathogenicity tests of two representative isolates (21BeanYC3-3 and 21BeanYC7-5) were performed on two-week-old healthy soybean seedlings (cv. Shengdou 101) by injecting and cutting root method with a conidial suspension (1×106 conidia per mL) of F. falciforme (2 mL to one seedling). Control seedlings were inoculated with 2 mL distilled water. After 40 days under 25℃, 16h light/8h dark, the root system of all inoculated soybean plants exhibited dark brown lesions over the entire taproot, while control plants remained healthy. The fungus was reisolated from inoculated plants and identified as F. falciforme based on morphological characteristics and molecular methods described above. To our knowledge, this is the first report of root rot in soybean (Glycine max L.) caused by F. falciforme in Henan, China. The results are important for soybean production and breeding programs.

Stable Layered 2D Perovskite Solar Cells with an Efficiency of over 19% via Multifunctional Interfacial Engineering.

Layered 2D perovskites have been extensively investigated by scientists with photovoltaics (PV) expertise due to their good environmental stability. However, a random phase distribution in the perovskite film could affect both the performance and stability of the devices. To overcome this problem, we propose multifunctional interface engineering of 2D GA2MA4Pb5I16 perovskite by employing guanidinium bromide (GABr) on top of it to optimize the secondary crystallization process. It is found that GABr treatment can facilitate to form a shiny and smooth surface of the 2D GA2MA4Pb5I16 film with excellent optoelectronic properties. Thus, we realize efficient and stable 2D perovskite solar cells (PSCs) with a champion power conversion efficiency (PCE) of 19.3% under AM 1.5G illumination. Additionally, the optimized device without encapsulation could retain 94% of the initial PCE for more than 3000 h after being stored under ambient conditions.

A joint method for the screening of pharmacological chaperones for phenylalanine hydroxylase.

Phenylalanine hydroxylase (PAH) deficiency (PAHD) is an autosomal recessive disorder that causes severe injury to the nervous system, the treatment of which mainly depends on dietary therapy. The limited treatment options for PAHD are an incentive to develop new methods to identify more efficient therapeutic drugs, such as agonists which could improve PAH activity. In this study, we aimed to establish a rapid and convenient method for the screening and verification of PAH agonists. We compared fluorospectrophotometry and tandem mass spectrometry for detection of enzymatic formation of tyrosine, finding that the latter was a more sensitive method. We optimized immunoprecipitation purification conditions and measurement conditions of PAH activity. The optimal ratio between PAH protein and magnetic beads was 500 µg protein per 20 µL beads, and the optimized conditions for the detection of PAH enzymatic activity included the presence of 75 µM coenzyme ((6R)-l-erythro-5,6,7,8-tetrahydrobiopterin) and 30 min reaction time. Based on virtual screening, we screened ten candidate agonists from the FDA drug library. Three of these (nefopam, fluocinonide, and risperidone) were found to activate the enzyme in a dose-dependent manner (0.1-10 µM) by the joint method. We tested the efficacy of the three agonists on three PAH mutations (p.I65T, p.H107R, and p.D101N) that influence enzyme activity, and found that risperidone could specifically activate D101N-mutated enzyme. In conclusion, we established a joint method that is highly reliable, cost-effective, labor-saving, and time-saving. And we also found a specific agonist for D101N-mutated PAH by this joint method which may assist the development of clinical treatment for PAHD patients with different enzyme deficiencies.

Relationship between amniotic fluid metabolic profile with fetal gender, maternal age, and gestational week.

BACKGROUND: Amniotic fluid (AF) provides vital information on fetal development, which is also valuable in identifying fetal abnormalities during pregnancy. However, the relationship between the metabolic profile of AF in the second trimester of a normal pregnancy with several maternal-fetal parameters remains poorly understood, which therefore limits its application in clinical practice. The aim of this study was to explore the association between the metabolic profile of AF with fetal gender, maternal age, and gestational week using an untargeted metabolomics method. METHODS: A total of 114 AF samples were analyzed in this study. Clinical data on fetal gender, maternal age, and gestational week of these samples were collected. Samples were analyzed by gas chromatography/time-of-flight-mass spectrometry (GC-TOF/MS). Principal component analysis(PCA), orthogonal partial least square discrimination analysis(OPLS-DA) or partial least square discrimination analysis (PLS-DA) were conducted to compare metabolic profiles, and differential metabolites were obtained by univariate analysis. RESULTS: Both PCA and OPLS-DA demonstrated no significant separation trend between the metabolic profiles of male and female fetuses, and there were only 7 differential metabolites. When the association between the maternal age on AF metabolic profile was explored, both PCA and PLS-DA revealed that the maternal age in the range of 21 to 40 years had no significant effect on the metabolic profile of AF, and only four different metabolites were found. There was no significant difference in the metabolic profiles of AF from fetuses of 17-22 weeks, and 23 differential metabolites were found. CONCLUSIONS: In the scope of our study, there was no significant correlation between the AF metabolic profile and the fetal gender, maternal age and gestational week of a small range. Nevertheless, few metabolites appeared differentially expressed.

Polarization enhancement of linearly polarized light through foggy environments at UV-NIR wavelengths.

Wavelength is an essential factor affecting polarization propagation. We investigate the polarization persistence of linearly polarized light from ultraviolet to near-IR in foggy environments. Certain spectral bands, from ultraviolet to IR wavelengths that exhibit lower path loss, were initially selected. Using polarization-tracking Monte Carlo simulations for varying particle size, wavelength, refractive index and detection range, it is shown that linear polarization exhibits different persistence performance at different wavelengths in various foggy environments. For wet haze of 0.6 µm or 1 µm droplets, parallel polarization increases persistently as the wavelength increases, and has superior persistence in the near-IR region. For radiation fog of 5 µm or 7.5 µm droplets, parallel polarization shows superior persistence in the ultraviolet region. For advection fog of 15 µm or 45 µm droplets, parallel polarization shows a superior persistence in the ultraviolet region. It is therefore shown that changing the wavelength can improve linear polarization persistence in foggy environments.

Eradication therapy for gastric cancer in Inner Mongolia: A single-center study over 10 years.

OBJECTIVE: To understand the characteristics, diagnosis and treatment of gastric cancer in a specific geographical region. METHODS: The retrospective study was conducted at the Affiliated Hospital of Inner Mongolia Medical University, China, and comprised clinical and pathological data of patients with gastric cancer treated from 2007 to 2017. Data was analysed according to the patients' ethnicity, gender, age, tumour location, differentiation degree, Bormann classification, tumour-nodes-metastases staging and pathological type. Statistical analysis was done using SPSS 22. RESULTS: Of the 2,049 patients, 1619(79.01%) were males and 430(20.99%) were females. The overall mean age of the sample was 60.94±10.90 years. The incidence of gastric antrum was the highest, with 830(40.51%) cases. The proportion of gastric cancers was different in different age groups (p=0.001). Of the total, 922(45%) cases were poorly differentiated adenocarcinoma. There were significant differences in the histological types of gastric cancer in different age groups (p=0.001). There were 130(6.3%) cases of Mongolian patients, and the composition ratio of each age group was not significantly different from that of Han ethnicity (p>0.05). However, location was different with 55(42.31%) cases involving oesophago-gastric junction. CONCLUSIONS: The diagnostic rate of gastric cancer in Western Inner Mongolia was relatively low. The incidence of gastric cancer among both Mongolian and Han patients was higher in elderly men. The incidence of gastric antrum was dominant in Han patients, followed by oesophago-gastric junction, while the reverse was true of Mongolian patients.

RNA sequencing analysis of long non-coding RNA expression in ocular posterior poles of guinea pig myopia models.

Purpose: To detect the differential expression of long non-coding RNAs (lncRNAs) in the ocular posterior poles of two guinea pig myopia models and explore the pathogenic role of lncRNAs in myopia. Methods: Form-deprived myopia (FDM) and lens-induced myopia (LIM) models were induced in guinea pig right eyes by wearing a translucent latex balloon head mask and a -10.00 diopter (D) lens, respectively. Ocular biometric parameters were measured biweekly. At 6 weeks after the induction of myopia, the guinea pig eyeballs were processed for hematoxylin and eosin staining to examine the ocular morphology. The ocular posterior poles from the normal control, FDM, and LIM groups were collected to analyze the differential expression of lncRNAs between the groups with high-throughput RNA sequencing (RNA-seq). Further, the lncRNA-mRNA colocation network was delineated to predict the functions of the differentially expressed lncRNAs. Last, Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the colocated mRNAs of the differentially expressed lncRNAs. Additionally, the expression of the most differentially expressed lncRNAs in the myopia-induced eyes and the contralateral eyes was validated with quantitative real-time PCR (qPCR). Results: Compared with the normal controls and the contralateral eyes, the myopia-induced eyes in the FDM and LIM groups exhibited decreased scleral and choroidal thicknesses, reduced refraction, and increased ocular axial length but without changes in the corneal curvature radius at 6 weeks after myopia was induced. RNA-seq showed that 372 and 247 lncRNAs were differentially expressed in the FDM and LIM groups, respectively, in comparison to the normal counterparts. There were 380 differentially expressed lncRNAs in the LIM group compared to the FDM group. The GO and KEGG analyses showed that the colocated mRNAs of the differentially expressed lncRNAs were enriched in cellular components such as the extracellular matrix (ECM) structural constituent; in molecular functions such as kinase activity, metabolism, and growth; as well as in pathways including ECM-receptor interaction, glycosaminoglycan degradation, and mucin type O-Glycan biosynthesis. The expression patterns of the selected lncRNAs were verified with qPCR. Conclusions: High-throughput RNA-seq revealed previously undescribed lncRNA expression profiling in guinea pig FDM and LIM models. These results may shed light on the molecular pathogenesis of myopia and provide clues for interventional targets for this highly prevalent visual disorder.