Clinical characteristics of two patients with neuronal intranuclear inclusion disease and literature review

BackgroundNeuronal intranuclear inclusion disease (NIID) is a rare chronic progressive neurodegenerative disease, with complex and diverse clinical manifestations and pathological eosinophilic hyaline intranuclear inclusions in the central and peripheral nervous systems and visceral organs. Improvements in diagnostic methods such as skin biopsy and gene testing are helpful in revealing the clinical and genetic characters of NIID.Materials and methodsWe presented two cases of NIID diagnosed by using NOTCH2NLC gene testing and skin biopsy. Diffusion weighted imaging (DWI) showed high linear intensity in corticomedullary junction. We also reviewed all the published NIID cases with positive NOTCH2NLC GGC repeat expansion and skin biopsy results in PubMed.ResultsPatient 1 was a 63-year-old male who carried 148 GGC repeats and presented with progressive tremor and limb weakness. Patient 2 was a 62-year-old woman who carried 131 GGC repeats and presented with tremors, memory loss and headaches. The most common clinical manifestation of 63 NIID patients in this study was cognitive impairment, followed by tremors. In our study, almost all the patients were from East Asia, the male to female ratio was 1:1.26, with an age of onset of 54.12 ± 14.12 years, and an age of diagnosis of 60.03 ± 12.21 years. Symmetrical high signal intensity at the corticomedullary junction on DWI were revealed in 80.96% of the patients. For the GGC repeat numbers, the majority of GGC repeats were in the 80–119 intervals, with few GGC repeats above 160. The number of GGC repetitions was significantly higher in patients presented with muscle weakness than in other clinical manifestations.ConclusionNIID is a neurodegenerative disease caused by aberrant polyglycine (polyG) protein aggregation. NIID mostly occurs in the elderly population in East Asia, with cognitive dysfunction as the most common symptom. Staging NIID based on clinical presentation is inappropriate because most patients with NIID have overlapping symptoms. In our study, there was no significant correlation between the number of GGC repeats and different phenotypes except for muscle weakness. Abnormal trinucleotides repeat and PolyG protein aggregation maybe common pathogenic mechanism in neurodegenerative diseases and cerebrovascular diseases, which needs to be confirmed by more studies

Jia-Wei-Kai-Xin-San treatment alleviated mild cognitive impairment through anti-inflammatory and antiapoptotic mechanisms in SAMP8 mice

Background. Alleviating mild cognitive impairment (MCI) is crucial to delay the progression of Alzheimer’s disease (AD). Jia-Wei-Kai-Xin-San (JWKXS) is applied for treating AD with MCI. However, the mechanism of JWKXS in the treatment of MCI is unclear. Thus, this study aimed to investigate the effect and mechanism of JWKXS in SAMP8 mice models of MCI. Methods. MCI models were established to examine learning and memory ability and explore the pathomechanisms in brain of SAMP8 mice at 4, 6, and 8 months. The mice were treated for 8 weeks and the effects of JWKXS on MCI were characterized through Morris water maze and HE/Nissl’s/immunohistochemical staining. Its mechanism was predicted by the combination of UPLC-Q-TOF/MS and system pharmacology analysis, further verified with SAMP8 mice, BV2 microglial cells, and PC12 cells. Results. It was found that 4-month-old SAMP8 mice exhibited MCI. Two months of JWKXS treatment improved the learning and memory ability, alleviated the hippocampal tissue and neuron damage. Through network pharmacology, four key signaling pathways were found to be involved in treatment of MCI by JWKXS, including TLR4/NF-κB pathway, NLRP3 inflammasome activation, and intrinsic and extrinsic apoptosis. In vitro and in vivo experiments demonstrated that JWKXS attenuated neuroinflammation by inhibiting microglia activation, suppressing TLR4/NF-κB and NLRP3 inflammasome pathways, and blocking the extrinsic and intrinsic apoptotic pathways leading to neuronal apoptosis suppression in the hippocampus. Conclusion. JWKXS treatment improved the learning and memory ability and conferred neuroprotective effects against MCI by inducing anti-inflammation and antiapoptosis. Limitations. The small sample size and short duration of the intervention limit in-depth investigation of the mechanisms. Future Prospects. This provides a direction for further clarification of the anti-AD mechanism, and provides certain data support for the formulation to move toward clinical practice

Aging Capacity of Wine and the Comparison of Four Antioxidant Capacity Assays

Aging capacity of wine is an essential facet of wine quality. It is widely accepted that wine oxidation is the main factor leading to the depletion of wine flavor and it limits the aging capacity of wine. During bottle aging, small amounts of air go through the cork or screw cap. Then, oxidation reactions are catalyzed by the iron(Ⅱ) and iron(Ⅲ) ions. The catechol phenols react with oxygen first which produces quinones and hydrogen peroxide. Then, hydrogen peroxide reacts with ethanol and yields acetaldehyde. The quinones and acetaldehyde alter the color and aroma characters of wine by reactions with important wine flavor substances and in the case of acetaldehyde giving oxidized aroma at high levels. SO2, ascorbic acid, and thiols are sacrificial antioxidants in wine that function by recycling the quinones back to catechol phenols, and in the case of SO2 by binding acetaldehyde, rendering it non-volatile. As a result, the antioxidants in wine contribute to the aging capacity of wine by reversing the effect of oxidation reactions. This research was performed with four antioxidant capacity assays, the SO2 addition method, an iron species assay, the DPPH assay and the FRAP assay, by testing commercial wine samples. FRAP assay and DPPH assay both respond to catechol phenols, SO2, thiols, and ascorbic acid in wine and reflects the overall antioxidant capacity of wine. The iron species method determines the antioxidant ability of wine by measuring the iron (Ⅱ) decreasing of the wine after air exposure. The SO2 addition method determines the SO2 in wine, such as weakly bound SO2, strongly bound SO2, and free SO2. Correlations among the four assays were studied understanding the relationships between the assays and shed light on how the reactions of each assay affected its ability to reveal the antioxidant capacity of the wine samples. Future direction of developing a new method to predicting the aging capacity of wine is elaborated

Can Chemical Analysis Predict Wine Aging Capacity?

Oxidation is the limiting factor in wine aging, and recently some famous wines have exhibited unexpected premature oxidation. Antioxidant assays may provide a means to assess a wine’s aging potential by measuring its capacity to chemically reduce reagent components. Correlations between antioxidant activity and wine components have the highest value with flavanols, notable for their catechol and phloroglucinol moieties. Both FRAP and DPPH based methods respond strongly to catechol groups, but these functional groups do not protect wine from oxidation. An ideal assay for wine aging capacity would respond selectively to thiols, phloroglucinol moieties, SO2 and other antioxidants capable of reducing quinones. A definitive test will be to compare the various assays against the shelf life of a number of commercial wines

Methanol to Propene over Gallium-Modified FAU Zeolite: Theoretical Study on the Polymethylbenzene and Alkene Cycles

The catalytic performance of gallium-modified acidic FAU (Ga-FAU) zeolite in the methanol to propene (MTP) process was theoretically investigated by a two-layer ONIOM (our own N-layered integrated molecular orbital and molecular Mechanics) method. The whole MTP mechanism includes two cycles: the polymethylbenzene (polyMB) cycle and the alkene cycle. The polyMB cycle consists of the direct internal H-shift pathway, spiro pathway, methyl-transfer pathway, and paring pathway. Compared with the previous theoretical results on the MTP process on the pure acidic Si/Al FAU, the addition of Ga atoms into the Si/Al H-FAU could reduce the contribution of the polyMB cycle and increase the reactivity of the alkene cycle on the MTP process. A careful analysis of activation free energy barriers on the transition states (TSs) shows that the internal H-shift step is the rate-determining step for the direct internal H-shift pathway and the paring pathway. The rate-determining step for the spiro and methyl-transfer pathways is the methylation of the PMB molecule. The methylation of the propene molecule is the rate-determining step for the alkene cycle. The polyMB and alkene cycles have almost the same reactivity on the Ga-FAU zeolite. For the polyMB cycle, the different elementary steps are in the following order of reactivity: internal methyl transfer > deprotonation > C–C bond cracking > ring contraction > methylation > internal H-shift. The order in the alkene cycle is different: deprotonation > proton transfer > beta-scission > methylation. The differential charge density (DCD), local orbital locator (LOL), and reduced density gradient (RDG) revealed the direction of electron flow in different fragments in the TS structures and the nature of interactions between the fragments in the TSs

Genetic correlation between female infertility and mental health and lifestyle factors: A linkage disequilibrium score regression study

Abstract Background and Aims Female fertility is a heterogeneous condition of complete psychosocial and physical well‐being. Observational studies have revealed that women with infertility have varying degrees of poor mental status and lifestyle choices in varying degrees. However, the genetic contribution to female infertility remains elusive. Our study aimed to explore the genetic correlations between female infertility and mental health and lifestyle factors. Methods The genome‐wide association study (GWAS) data sets of characteristics related to mental health and lifestyle were obtained from the IEU OpenGWAS database. The GWAS data sets of female infertility were derived from the Finggen database. Linkage disequilibrium score regression was performed to systematically estimate the pairwise genetic correlations between female infertility and a set of mental health‐ and lifestyle‐related traits. Results The genetic correlation analysis revealed a moderate and positive genetic correlation between depressive symptoms, major depressive disorder, and female infertility. Similarly, worry and the personality trait of neuroticism displayed a moderate positive genetic correlation with female infertility. Adversely, a negative and moderate genetic correlation was observed between strenuous sports or exercises and female infertility. Conclusion The study demonstrated genetic correlations between female infertility and mental health status, including depression, worry, and neuroticism. Additionally, we observed that females with better physical activity may have reduced risks of female infertility. These findings would serve as a fundamental resource for understanding the genetic mechanisms of the effects of mental health and lifestyle factors on female infertility

Effects of Grazing Intensity on the Carbon, Nitrogen and Phosphorus Content, Stoichiometry and Storage of Plant Functional Groups in a Meadow Steppe

Studies on the impacts of grazing on carbon, nitrogen, and phosphorus stoichiometry and storage are crucial for better understanding the nutrient cycles of grasslands ecosystems. Using a controlled grazing experimental platform in a meadow steppe ecosystem, the effects of different stocking rates (0.00, 0.23, 0.34, 0.46, 0.69, and 0.92 AU ha−1) on the carbon, nitrogen, and phosphorus contents of plant functional groups were explored. The major results were: (1) The carbon content of Gramineae Barnhart was significantly reduced by grazing intensity (p Cyperaceae Rotundus was significantly higher than that of the other groups; the total nitrogen content of Cyperaceae and other groups and total phosphorus contents of Gramineae, Leguminosae Sp., Cyperaceae, and other groups all increased significantly with increasing grazing intensity (p Gramineae, Leguminosae, and Ranunculaceae L. decreased significantly with increasing grazing intensity. Heavy grazing reduced the carbon, nitrogen, and phosphorus storage amounts of Cyperaceae and other groups, while the carbon, nitrogen, and phosphorus storage amounts of Compositae were the largest under moderate grazing. (3) The nitrogen content of each functional group was highly significantly negatively correlated with the C/N ratio, and the phosphorus content was highly significantly negatively correlated with the C/P ratio. Grazing and foraging affected the growth of the different functional groups, which in turn affected their carbon, nitrogen, and phosphorus content, stoichiometry, and storage. Moderate grazing improved the nutrient utilization efficiency of grassland and is beneficial for promoting sustainable grassland development

Response of Temperate <i>Leymus chinensis</i> Meadow Steppe Plant Community Composition, Biomass Allocation, and Species Diversity to Nitrogen and Phosphorus Addition

Studies on the impacts of fertilization on plant production and species diversity are crucial for better maintaining the stability of grassland ecosystems and restoring degraded grasslands. Using a controlled fertilization experimental platform in a temperate Leymus chinensis meadow steppe ecosystem, the effects of different levels of nitrogen (N) and phosphorus (P) addition on plant community structure, biomass allocation, diversity, and the correlation relationship were explored. The major results were as follows: (1) The structural composition of the plant community changed after different levels of N and P addition; the dominance ratio and biomass of Poaceae plants increased gradually with increasing N and P addition levels. (2) The addition of N and P increased the height, density and coverage of the plant community, the biomass of the dominant L. chinensis and plant community and the total productivity of grassland, and reduced the root–shoot ratio of grassland biomass. For example, plant community biomass, gramineous plant biomass and grassland total productivity increased by 84.46–204.08%, 162.64–424.20%, and 38.12–46.44%, respectively, after N and P addition. (3) The community richness, diversity, and evenness indices decreased overall and showed binomial regression after N and P addition; the functional group of Poaceae plants was highly significantly negatively correlated with species diversity indices and was highly significantly positively correlated with the aboveground biomass of L. chinensis and community; Leguminosae plants and Ranunculaceae plants were highly significantly positively correlated with Margalef and Patrick richness indices; Ranunculaceae plants were highly significantly and negatively correlated with L. chinensis biomass, community biomass, and Poaceae plants. Moderate fertilization not only improved the plant community structure and productivity but was also beneficial for maintaining the grassland species diversity and stability

Genetic Mapping of Grain Shape Associated QTL Utilizing Recombinant Inbred Sister Lines in High Yielding Rice (Oryza sativa L.)

Grain shape is a key factor for yield and quality in rice. To investigate the genetic basis of grain shape in the high-yielding hybrid rice variety Nei2You No.6, a set of recombinant inbred sister lines (RISLs) were used to map quantitative trait loci (QTLs) determining grain length (GL), grain width (GW), and length-width ratio (LWR) in four environments. A total of 91 medium/minor-effect QTL were detected using a high-density genetic map consisting of 3203 Bin markers composed of single nucleotide polymorphisms, among which 64 QTL formed 15 clusters. Twelve of 15 clusters co-localized with QTL previously reported for grain shape/weight. Three new QTL were detected: qGL-7a, qGL-8, and qGL-11a. A QTL cluster, qLWR-12c/qGW-12, was detected across all four environments with phenotypic variation explained (PVE) ranging from 3.67% to 11.93%, which was subsequently validated in paired lines of F17 progeny and tightly linked marker assay in F10 generation. Subsequently, 17 candidate genes for qLWR-12c/qGW-12 were detected in the 431 Kb interval utilizing bulk segregant analysis (BSA). Among these, OsR498G1222170400, OsR498G1222171900, OsR498G1222185100, OsR498G1222173400, and OsR498G1222170500 were the best candidates, which lays the foundation for further cloning and will facilitate high-yield breeding in rice

Finding Stable QTL for Plant Height in Super Hybrid Rice

Plant height (PH) is one of the most important agronomic traits determining plant architecture in rice. To investigate the genetic basis of plant height in the high-yielding hybrid rice variety Nei2You No.6, recombinant inbred sister lines (RISLs) were used to map quantitative trait loci (QTL) over four years. A total of 19 minor/medium-effect QTLs were mapped on eleven chromosomes except chromosome 10, totally explaining 44.61&ndash;51.15% phenotypic variance in four environments. Among these, qPH-1a, qPH-1b, qPH-2b, qPH-3b, qPH-6, and qPH-7b were repeatedly detected over four years. Among these, the qPH-6 was mapped to an interval of 22.11&ndash;29.41 Mb on chromosome 6L, which showed the highest phenotypic variation explained (PVE) of 10.22&ndash;14.05% and additive effect of 3.45&ndash;4.63. Subsequently, evaluation of near isogenic lines (NILs) showed that the qPH-6 allele from the restorer line (R8006) could positively regulate plant height, resulting in an 18.50% increase in grain yield. These results offered a basis for further mapping of qPH-6 and molecular breeding in improving plant architecture in rice