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Inclusions comprised of microtubule-associated protein tau (tau) are implicated in a group of neurodegenerative diseases, collectively known as tauopathies, that include Alzheimer’s disease (AD). The spreading of misfolded tau “seeds” along neuronal networks is thought to play a crucial role in the progression of tau pathology. Consequently, restricting the release or uptake of tau seeds may inhibit the spread of tau pathology and potentially halt the advancement of the disease. Previous studies have demonstrated that the Mammalian Suppressor of Tauopathy 2 (MSUT2), an RNA binding protein, modulates tau pathogenesis in a transgenic mouse model. In this study, we investigated the impact of MSUT2 on tau pathogenesis using tau seeding models. Our findings indicate that the loss of MSUT2 mitigates human tau seed-induced pathology in neuron cultures and mouse models. In addition, MSUT2 regulates many gene transcripts, including the Adenosine Receptor 1 (A1AR), and we show that down regulation or inhibition of A1AR modulates the activity of the “ArfGAP with SH3 Domain, Ankyrin Repeat, and PH Domain 1 protein” (ASAP1), thereby influencing the internalization of pathogenic tau seeds into neurons resulting in reduction of tau pathology. [ABSTRACT FROM AUTHOR]

To understand the epidemiological and genetic characteristics of B19V, a multiple-province surveillance of patients with febrile rash illnesses (FRIs) were conducted in China during 2009 ~ 2021. The clinical specimens of 3,820 FRI patients were collected and tested for B19V DNA. A total of 99 (2.59%) patients were positive for B19V, and 49 (49.49%) were children under 5 years old. B19V infections occurred throughout the year without obvious seasonal pattern. Ten NS1-VP1u sequences and seven genome sequences were obtained in this study, identified as subgenotype 1a. Combined with the globally representative genome sequences, no temporal and geographic clustering trends of B19V were observed, and there was no significant correlation between B19V sequences and clinical manifestations. The evolutionary rate of the B19V genome was 2.30 × 10–4 substitutions/site/year. The number of negative selection sites was higher than that of positive selection sites. It was the first to comprehensively describe the prevalence patterns and evolutionary characteristics of B19V in FRI patients in China. B19V played the role in FRI patients. Children under 5 years old were the main population of B19V infection. Subgenotype 1a was prevalent in FRI patients in China. B19V showed a high mutation rate, while negative selection acted on the genome. [ABSTRACT FROM AUTHOR]

To understand the epidemiological and genetic characteristics of B19V, a multiple-province surveillance of patients with febrile rash illnesses (FRIs) were conducted in China during 2009 ~ 2021. The clinical specimens of 3,820 FRI patients were collected and tested for B19V DNA. A total of 99 (2.59%) patients were positive for B19V, and 49 (49.49%) were children under 5 years old. B19V infections occurred throughout the year without obvious seasonal pattern. Ten NS1-VP1u sequences and seven genome sequences were obtained in this study, identified as subgenotype 1a. Combined with the globally representative genome sequences, no temporal and geographic clustering trends of B19V were observed, and there was no significant correlation between B19V sequences and clinical manifestations. The evolutionary rate of the B19V genome was 2.30 × 10–4 substitutions/site/year. The number of negative selection sites was higher than that of positive selection sites. It was the first to comprehensively describe the prevalence patterns and evolutionary characteristics of B19V in FRI patients in China. B19V played the role in FRI patients. Children under 5 years old were the main population of B19V infection. Subgenotype 1a was prevalent in FRI patients in China. B19V showed a high mutation rate, while negative selection acted on the genome. [ABSTRACT FROM AUTHOR]

Purpose: To determine the association between ammonium concentration in culture medium and blastocyst development and to assess the influence of increased ammonium concentration on the expression of Bax, Bcl-2 and Oct4. Methods: A total of 254 cleavage-stage embryos were individually cultured in 30μL G2-plus medium on Day 3, and then culture media samples were collected on Day 5 for ammonium concentration determination immediately after evaluating the embryos morphology. Poor-quality blastocysts (combined score of CC) were used for gene expression analysis. The blastocyst formation rate, good-quality blastocyst rate and relative expression levels of Bax, Bcl-2 and Oct4 were analyzed. Results: Based on receiver operating characteristic curve, the cutoff value of ammonium concentration produced by embryos was 16.07 μmol/L (AUC = 0.722, 95% CI 0.637–0.807; P = 0.000), so all embryos were assigned to two groups according to the cutoff value: normal group (< 16.07 μmol/L) and increased group (≥ 16.07 μmol/L). There was a significant difference in blastocyst formation rate (80.5% vs 59.0%, P < 0.01) between normal group and increased group, as well as for good-quality blastocyst rate (21.0% vs 3.4%, P < 0.01). A significantly higher expression level of Bax (P < 0.05) and considerably lower expression level of Oct4 (P < 0.01) were observed in increased group compared to normal group. Conclusion: Our data demonstrated for the first time that increased ammonium concentration in culture medium may promote cellular apoptosis and negatively affect pluripotency of human blastocyst. [ABSTRACT FROM AUTHOR]

Objective: Patients with gastric atrophy and intestinal metaplasia (IM) were at risk for gastric cancer, necessitating an accurate risk assessment. We aimed to establish and validate a diagnostic approach for gastric biopsy specimens using deep learning and OLGA/OLGIM for individual gastric cancer risk classification. Methods: In this study, we prospectively enrolled 545 patients suspected of atrophic gastritis during endoscopy from 13 tertiary hospitals between December 22, 2017, to September 25, 2020, with a total of 2725 whole-slide images (WSIs). Patients were randomly divided into a training set (n = 349), an internal validation set (n = 87), and an external validation set (n = 109). Sixty patients from the external validation set were randomly selected and divided into two groups for an observer study, one with the assistance of algorithm results and the other without. We proposed a semi-supervised deep learning algorithm to diagnose and grade IM and atrophy, and we compared it with the assessments of 10 pathologists. The model's performance was evaluated based on the area under the curve (AUC), sensitivity, specificity, and weighted kappa value. Results: The algorithm, named GasMIL, was established and demonstrated encouraging performance in diagnosing IM (AUC 0.884, 95% CI 0.862–0.902) and atrophy (AUC 0.877, 95% CI 0.855–0.897) in the external test set. In the observer study, GasMIL achieved an 80% sensitivity, 85% specificity, a weighted kappa value of 0.61, and an AUC of 0.953, surpassing the performance of all ten pathologists in diagnosing atrophy. Among the 10 pathologists, GasMIL's AUC ranked second in OLGA (0.729, 95% CI 0.625–0.833) and fifth in OLGIM (0.792, 95% CI 0.688–0.896). With the assistance of GasMIL, pathologists demonstrated improved AUC (p = 0.013), sensitivity (p = 0.014), and weighted kappa (p = 0.016) in diagnosing IM, and improved specificity (p = 0.007) in diagnosing atrophy compared to pathologists working alone. Conclusion: GasMIL shows the best overall performance in diagnosing IM and atrophy when compared to pathologists, significantly enhancing their diagnostic capabilities. [ABSTRACT FROM AUTHOR]

Based on a fluoran skeleton, we herein reported a new fluorescent probe FLACu for Cu2+ by facile modification of the spirolactone of dye 1 with phenylhydrazine. Taking advantage of the spirolactam moiety, FLACu only delivers a specific "off-on" fluorescence signal output towards Cu2+ when treated with various metal ions, which has been well elucidated as the result of spirolactam ring opening and hydrolysis processes induced by copper ion. Meanwhile, the limit of detection (LOD) for FLACu has been estimated to be 35.4 nM and a pH range of 5.0–9.0 is evaluated to be suitable for Cu2+ detection. Significantly, FLACu shows low cell cytotoxicity and can be further ultilzied in the detection of exogenous Cu2+ in the living Hela cells. [ABSTRACT FROM AUTHOR]

Astroviruses (AstVs) have a very wide range of hosts and are associated with enteric and extra-enteric disease in mammals and birds. Cross-species transmission of AstVs has been observed frequently. In the present study, the genome of a novel astrovirus from Amur tigers (Panthera tigris) from a zoo in China was characterized and was found to have the typical genomic features of other mammal AstVs. It showed the highest nucleotide sequence similarity (46.1-87.3% identity) to AstVs from cats, indicating a close phylogenetic relationship and possible cross-species transmission between them. To our knowledge, this is the first identification and characterization of AstV from tigers, and this virus is the third astrovirus identified in hosts of the family Felidae. The results of this study will be helpful for understanding the origin, genetic diversity, and cross-species transmission of AstV. [ABSTRACT FROM AUTHOR]

GABA is a dominant inhibitory neurotransmitter in the brain and A type GABA receptor (GABAAR) phosphorylation is critical for GABA-mediated inhibitory effect. However, its role in the neuroprotective effect of sodium valproate (VPA), a prevalent drug for treating patients with epilepsy, remains elusive. The present study was conducted to explore the role of GABAAR phosphorylation in the neuroprotection of VPA against a kainic acid-induced epileptic rat model and the potential molecular mechanisms. Neuronal apoptosis was evaluated by TUNEL assay, PI/Annexin V double staining, caspase-3 activity detection and Bax and Bcl-2 proteins expression via Western blot analysis. The primary rat hippocampal neurons were cultivated and cell viability was measured by CCK8 detection following KA- or free Mg2+-induced neuronal impairment. Our results found that VPA treatment significantly reduced neuronal apoptosis in the KA-induced rat model (including reductions of TUNEL-positive cells, caspase-3 activity and Bax protein expression, and increase of Bcl-2 protein level). In the in vitro experiments, VPA at the concentration of 1 mM for 24 h also increased cell survival and suppressed cell apoptosis in KA- or no Mg2+-induced models via CCK8 assay and PI/Annexin V double staining, respectively. What is more important, the phosphorylation of γ2 subunit at serine 327 residue for GABAAR was found to be robustly enhanced both in the KA-induced epileptic rat model and neuronal cultures following KA exposure after VPA treatment, while no evident alteration was found in terms of GABAAR β3 phosphorylation (408 or 409 serine residue). Additionally, pharmacological inhibition of protein kinase C (PKC) clearly abrogated the neuroprotective potential of VPA against KA- or free Mg2+-associated neuronal injury, indicating a critical role of PKC in the effect of GABAAR γ2 serine 327 phosphorylation in VPA’s protection. In summary, our work reveals that VPA mitigates neuronal apoptosis in KA-triggered epileptic seizures, at least, via augmenting PKC-dependent GABAAR γ2 phosphorylation at serine 327 residue. [ABSTRACT FROM AUTHOR]

Monocular vision system is widely used in many fields due to its simple structure, faster speed, and lower cost for object measurement. However, most of the current monocular methods have complicated mathematical models or require artificial markers to achieve accurate measurement results. In addition, it is not easy to precisely extract the features of objects in the captured image which are affected by many factors. In this paper, we present a semantic-aware monocular projection model for accurate pose measurement. Our mathematical model is simple and neat, and we use deep learning network to extract the semantic features in images. Finally, the relevant parameters of the projection model are further optimized with Kalman filter to make the measurement results more accurate and stable. The extensive experiments demonstrate that the proposed method is robust with high performance and accuracy. As a few constraints are required on the measured object and environment, our method is easy for installation. [ABSTRACT FROM AUTHOR]

In this paper, the design challenges of the injection-locked oscillator (ILO)-based phase shifter are reviewed and analyzed. The key design considerations such as the operating frequency, locking range, and linearity of the phase shifters are analysed in detail. It is possible to optimize the phase shifter in certain parameters such as ultra-low power while meeting the requirements of a certain system. As a design example, a K-band phase shifter is implemented using a commercial 0.13 μm CMOS technology, where a conventional LC tank based topology is implemented but optimised with a good balance among power consumption, working range, sensitivity, and silicon area, etc. Measurement results show that the proposed phase shift is able to work at 22-23.4 GHz with a range of 180 while consuming 3.14 mW from a 1.2 V supply voltage. [ABSTRACT FROM AUTHOR]

Objectives: To compare the clinical and MRI features of primary hepatic lymphoepithelioma-like carcinoma (LELC) categorized as LR-M or LR-4/5 using the Liver Imaging Reporting and Data System (LI-RADS) version 2018 and to determine the prognostic factors for recurrence-free survival (RFS). Methods: In this retrospective study, 37 patients with surgically confirmed LELC were included. Two independent observers evaluated preoperative MRI features according to the LI-RADS version 2018. Clinical and imaging features were compared between two groups. RFS and the associated factors were evaluated using Cox proportional hazards regression analysis, Kaplan–Meier analysis, and log-rank test. Results: In total, 37 patients (mean age, 58.5 ± 10.3 years) were evaluated. Sixteen (43.2%) LELCs were categorized as LR-M and twenty-one (56.8%) LELCs were categorized as LR-4/5. In the multivariate analysis, the LR-M category was an independent factor for RFS (HR 7.908, 95% CI 1.170–53.437; p = 0.033). RFS rates were significantly lower in patients with LR-M LELCs than in patients with LR-4/5 LELCs (5-year RFS rate, 43.8% vs.85.7%; p = 0.002). Conclusion: The LI-RADS category was significantly associated with postsurgical prognosis of LELC, with tumor categorized as LR-M having a worse RFS than those categorized as LR-4/5. Key Points: • Lymphoepithelioma-like carcinoma patients categorized as LR-M have worse recurrence-free survival than those categorized as LR-4/5. • MRI-based LI-RADS categorization was an independent factor for postoperative prognosis of primary hepatic lymphoepithelioma-like carcinoma. [ABSTRACT FROM AUTHOR]

Adenovirus type 5 (Ad5) specifically binds coagulation factor X (FX), and FX is normally essential for intravenously injected Ad5 vectors to transduce the liver. We demonstrate that the ability of FX to enhance liver transduction by Ad5 vectors is due to an unexpected ability of FX to protect Ad5 from attack by the classical complement pathway. In vitro, naive mouse serum neutralized Ad5 when FX was blocked from binding Ad5. This neutralization was mediated by natural IgM and the classical complement pathway. In vivo, FX was essential for Ad5 vectors to transduce the livers of wild-type mice, but FX was not required for liver transduction in mice that lack antibodies, C1q or C4. We conclude that Ad5 recruits FX as a defense against complement and that the sensitivity of Ad5 to inactivation by complement must be taken into account when designing vectors for systemic gene therapy. [ABSTRACT FROM AUTHOR]

Methotrexate (MTX) is widely used and considered a first-line disease modifying anti-rheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). Many of the relevant genes have been investigated to estimate the association between gene polymorphisms and MTX effectiveness in RA patients, although inconsistent results have been reported. A systematic review and meta-analysis were performed to identify genetic variants associated with MTX efficacy. A total of 30 publications that included 34 genes and 125 SNPs associated with the transporters, enzymes, and metabolites of MTX or the progression of RA were included in the systematic review (SR), and 21 studies were included in 9 meta-analyses. Associations between MTX response in RA patients in MTHFR 1298A > C (rs1801131), ATIC 347C > G (rs2372536), RFC-1 80G > A (rs1051266), SLC19A1 A > G (rs2838956) and SLC19A1 G > A (rs7499) genetic polymorphisms were found, but not observed between the MTHFR 677C > T (rs1801133), TYMS 28 bp VNTR (rs34743033), MTRR 66A > G (rs1801394), and ABCB1 3435C > T (rs1045642). However, for the polymorphisms not being associated following meta-analysis could still be associated if larger cohorts were used, and studies of other polymorphisms are necessary in large cohorts and a rigorous way, which may provide more accurate results for the effect of the gene polymorphisms on the MTX response. [ABSTRACT FROM AUTHOR]

Difflugia tuberspinifera, a testate amoeba found in the open water plankton of Liuxi He and other south Chinese reservoirs during summer, is one of six or more species that occasionally live a pelagic life. Here, we suggest that its incentive to leave the bottom might be the abundance of food in the water column rather than temperature. This Difflugia (and perhaps the other pelagic species as well) is indeed an actively hunting carnivore that catches small rotifers and other prey in the same size range. In Liuxi He, it readily feeds on Collotheca cf. mutabilis, which it catches and consumes with remarkable agility: it first inspects the jelly tube that protects the prey, then moves to the bottom of it, perforates the jelly near the prey’s foot, and finally ingests the rotifer foot-first. [ABSTRACT FROM AUTHOR]

A new biscarbazole-fused xanthene hybrid dye MeBCX has been prepared by CH3SO3H-promoted condensation of 4-hydroxycarbazole and o-phthalic anhydride, followed by esterification with methanol, which exhibits good cell membrane permeability. Taking advantage of the spiro-controlled xanthene platform of the dye, a Cu2+-selective fluorescence "off-on" probe BCX-Cu has been successfully prepared with excellent performances in selectivity and sensitivity, and the detection limit is calculated to be 88.7 nM. The sensing mechanism is confirmed to involve a specific cascade reactions of Cu2+-induced spirolactam ring-opening and hydrolysis. In addition, living L929 cell imaging demonstrates the probe has living cell membrane permeability and shows great potential for tracing intracellular Cu2+ through fluorescence imaging technology. [ABSTRACT FROM AUTHOR]

The process technologies for conversion of bio-feedstocks such as vegetable oils, animal fats, and algal oil into renewable diesel have been developed and commercialized during the last decade. The global annual production capacity of renewable diesel is approaching to 5.5 million tons per year. The refining process generally includes pretreatment of the renewable feedstock to remove impurities, hydroprocessing and isomerization to produce hydrocarbons, and distillation to produce a fuel suitable for use as diesel or jet fuel. This article reviews recent development in the commercial production of renewable diesel, pretreatment technologies, chemistry of deoxygenation and cracking of triglycerides, the effect of reaction parameters on the relative activities of different reaction pathways, catalyst development, and the technical details of commercial processes for refining bio-feedstocks. [ABSTRACT FROM AUTHOR]

Objective: To screen differentially expressed lncRNAs involved in OHSS. OHSS is defined as ovarian hyperstimulation syndrome. It is characterized as enlarged ovary and increased vascular permeability.Design: Case-control study.Setting: University-affiliated hospital.Patient(s): Patients with OHSS high risk (n = 30) and low risk (n = 30) were included in this study.Intervention(s): None.Main outcome measure(s): LncRNAs from women with OHSS high risk and low risk were used for high-throughput sequencing profiling. The eight most differentially expressed lncRNAs in granulosa cells were validated by semi-quantitative reverse transcription-polymerase chain reaction analysis.Result(s): A total of 23,815 lncRNAs were detected and 482 were differentially expressed (fold-change ≥2; p < 0.05, FDR value < 0.001), of which 205 were upregulated and 277 were downregulated. Lnc-SEC16B.1-6, lnc-SNURF-13, lnc-LGR6-6, and lnc-H2AFY2-2 were up-regulated, while lnc-BRD2-2, lnc-HSPA6-2, and lnc-CLIC6-5 were downregulated significantly in granulosa cells. These results were confirmed by qRT-PCR. KEGG pathways and Gene Ontology enrichment analysis revealed that several biological processes were significantly associated. Meanwhile, the lncRNA/miRNA interaction network was established according to ceRNA network model.Conclusion(s): Comprehensive expression screening identified eight novel lncRNAs associated with risk factors of OHSS process. Although it is unclear how these altered lncRNAs regulate the process of OHSS, our findings suggest these lncRNAs may be novel players in OHSS development. [ABSTRACT FROM AUTHOR]

The effect of coatings (Y2O3, ZrO2 and Al2O3) on the interfacial reaction of TiAl alloys was studied with molecular dynamics. The binding energy of coatings and the diffusion process of oxygen in the melt were simulated, and then the simulation results were compared with the experimental results. The simulation results indicate that for each of the three simulated coatings, inordinate interfacial reactions have occurred between the coating and the melt. The binding energy results show that Y2O3 has the best stability and is the most difficult to break down. ZrO2 has the greatest decomposition energy and is the easiest to break down in the melt. Besides, the molecular dynamics indicate that the diffusion coefficient of the oxygen atom in Al2O3 is larger than that in the other two coatings, indicating that oxygen diffusion in Al2O3 is the fastest at a given temperature. The experimental results show that the oxygen concentration of the melt with Al2O3 coating is the highest, and the oxygen diffusion is of similar magnitude to the simulation values, from which the conclusion can be obtained that the oxygen concentration is significantly influenced by the coating materials. [ABSTRACT FROM AUTHOR]

The reprogramming of epigenetic states in gametes and embryos is essential for correct development in plants and mammals. In plants, the germ line arises from somatic tissues of the flower, necessitating the erasure of chromatin modifications that have accumulated at specific loci during development or in response to external stimuli. If this process occurs inefficiently, it can lead to epigenetic states being inherited from one generation to the next. However, in most cases, accumulated epigenetic modifications are efficiently erased before the next generation. An important example of epigenetic reprogramming in plants is the resetting of the expression of the floral repressor locus FLC in Arabidopsis thaliana. FLC is epigenetically silenced by prolonged cold in a process called vernalization. However, the locus is reactivated before the completion of seed development, ensuring the requirement for vernalization in every generation. In contrast to our detailed understanding of the polycomb-mediated epigenetic silencing induced by vernalization, little is known about the mechanism involved in the reactivation of FLC. Here we show that a hypomorphic mutation in the jumonji-domain-containing protein ELF6 impaired the reactivation of FLC in reproductive tissues, leading to the inheritance of a partially vernalized state. ELF6 has H3K27me3 demethylase activity, and the mutation reduced this enzymatic activity in planta. Consistent with this, in the next generation of mutant plants, H3K27me3 levels at the FLC locus stayed higher, and FLC expression remained lower, than in the wild type. Our data reveal an ancient role for H3K27 demethylation in the reprogramming of epigenetic states in plant and mammalian embryos. [ABSTRACT FROM AUTHOR]

To improve the working condition of liquid crystal phase shifter on incident laser power, a theoretical model on laser induced phase distortion is built on the physics of heat deposition and heat transfer. Four typical factors (absorption, heat sink structure, cooling fluid rate, and substrate) are analyzed to evaluate the influence of phase distortion when a relative high-power laser is pumped into the liquid crystal phase shifter. Flow rate of cooling fluid and heat sink structure are the most important two factors on improving the limit of incident laser power. Meanwhile, silicon wafer is suggested to replace the back glass contacting the heat sink, because of its higher heat transfer coefficient. If the device is fabricated on the conditions that: the total absorption is 5% and it has a strong heat sink structure with a flow rate of 0.01 m/s, when the incident laser power is 110W, the laser-induced phase deformation on the center is diminished to be less than 0.06, and the maximum temperature increase on the center is less than 1K degree. [ABSTRACT FROM AUTHOR]