Interactive Effects of Methionine and Lead Intake on Cognitive Function among Chinese Adults.

The association between methionine intake and cognitive function is inconclusive. We aimed to assess the association between methionine intake and cognitive function in Chinese adults and to explore the interaction between methionine and lead intake. Data from 4852 adults aged ≥55 years from the China Health and Nutrition Survey were used. Cognitive function was measured in 1997, 2000, 2004, and 2006. A 3-day, 24-hour recall was used to assess methionine and lead intake from different protein sources. Multivariable mixed linear regression was used in the analyses. Total methionine intake was positively correlated with cognition. There was a significant interaction between animal methionine and lead intakes. In subgroup analyses, across the quartiles of animal methionine intake, the regression coefficients (95% CI) for global cognition were 0.00, 0.57 (0.17 to 0.98), 1.18 (0.73 to 1.62), and 1.80 (1.31 to 2.29), respectively, while they were 0.00, -0.73 (-1.12 to -0.34), -0.83 (-1.26 to -0.41), and -1.72 (-2.22 to -1.22) across the quartiles of plant methionine intake, respectivelyThe association between animal methionine intake and cognition was stronger among adults with a low lead intake. In conclusion, animal methionine and plant methionine intake were positively and inversely associated with cognition, respectively. Lead intake modified the association between animal methionine intake and cognition.This study was supported in part by research grants from the Natural Scientific Foundation in Qinghai Province (2019-ZJ-932Q), and the National Key Research and Development Program of China (grant numbers: 2017YFC0907200 and 2017YFC0907201)

Comprehensive analysis of grazing intensity impacts alpine grasslands across the Qinghai-Tibetan Plateau: A meta-analysis

Livestock grazing is a dominant practice in alpine grasslands and plays a crucial role in the ecosystem service of the Qinghai-Tibetan Plateau. The effects of grazing on alpine grasslands highly depends on grazing intensity. Up to now, we still lack comprehensive understanding of the general responses of alpine grasslands to different grazing intensities over broad geographic scales across the Qinghai-Tibetan Plateau. Here, we conducted a meta-analysis to explore the responses of plant characteristics and soil properties to grazing intensity in alpine grasslands of the Qinghai-Tibetan Plateau based on 52 peer-reviewed literatures. The results showed that grazing did not change the belowground biomass, while significantly increased the ratio of root to shoot (P< 0.05). Light grazing exhibited no significant effects on the plant richness, Shannon-Wiener diversity, soil water content, soil bulk density, nutrients, microbial biomass carbon, and microbial biomass nitrogen (P > 0.05). Moderate grazing significantly increased the plant richness and Shannon-Wiener diversity, while significantly decreased the soil organic carbon and total nitrogen (P< 0.05). Heavy grazing significantly decreased the plant richness, Shannon-Wiener diversity, water content, soil organic carbon, total nitrogen, microbial biomass carbon, and microbial biomass nitrogen, and significantly increased the soil bulk density (P< 0.05). These findings suggest that overgrazing is closely associated with grassland degradation, and moderate grazing is a sustainable practice to provide animal production and simultaneously maintain ecological functions for alpine grasslands on the Qinghai-Tibetan Plateau

Molecular and biochemical investigations of the anti-fatigue effects of tea polyphenols and fruit extracts of Lycium ruthenicum Murr. on mice with exercise-induced fatigue

Background: The molecular mechanisms regulating the therapeutic effects of plant-based ingredients on the exercise-induced fatigue (EIF) remain unclear. The therapeutic effects of both tea polyphenols (TP) and fruit extracts of Lycium ruthenicum (LR) on mouse model of EIF were investigated.Methods: The variations in the fatigue-related biochemical factors, i.e., lactate dehydrogenase (LDH), superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-2 (IL-2), and interleukin-6 (IL-6), in mouse models of EIF treated with TP and LR were determined. The microRNAs involved in the therapeutic effects of TP and LR on the treatment of mice with EIF were identified using the next-generation sequencing technology.Results: Our results revealed that both TP and LR showed evident anti-inflammatory effect and reduced oxidative stress. In comparison with the control groups, the contents of LDH, TNF-α, IL-6, IL-1β, and IL-2 were significantly decreased and the contents of SOD were significantly increased in the experimental groups treated with either TP or LR. A total of 23 microRNAs (21 upregulated and 2 downregulated) identified for the first time by the high-throughput RNA sequencing were involved in the molecular response to EIF in mice treated with TP and LR. The regulatory functions of these microRNAs in the pathogenesis of EIF in mice were further explored based on Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses with a total of over 20,000–30,000 target genes annotated and 44 metabolic pathways enriched in the experimental groups based on GO and KEGG databases, respectively.Conclusion: Our study revealed the therapeutic effects of TP and LR and identified the microRNAs involved in the molecular mechanisms regulating the EIF in mice, providing strong experimental evidence to support further agricultural development of LR as well as the investigations and applications of TP and LR in the treatment of EIF in humans, including the professional athletes

The Association between Methionine Intake and Diabetes in Chinese Adults-Results from the China Health and Nutrition Survey

This study aimed to evaluate the association between methionine intake and diabetes prevalence in Chinese adults and explore whether the association was source-specific. Data from 12,849 adults aged ≥20 years old were used from the China Health and Nutrition Survey during 1997–2011. Diabetes was diagnosed as self-reported and/or when blood tests results met the diagnostic criteria. A 3-day, 24-h recall was used to assess different sources of methionine. Multivariable mixed linear regression was used to examine the associations. Across the quartiles of total methionine intake, the odds ratio (ORs, 95% CI) of diabetes were 1.00, 1.49 (1.21 to 1.82), 1.72 (1.37 to 2.15), and 2.53 (1.97 to 3.23). In the subgroup analysis, similar trends were observed in both animal and plant methionine. There was a significant interaction between urbanization and diabetes. The positive association was only significant in those who lived in low or medium urbanization areas. The ORs (95% CI) were 1.00, 1.27 (0.85 to 1.88), 1.56 (1.01 to 2.39), and 1.79 (1.09 to 2.95) for medium urbanization, respectively. No interaction was identified when stratified by different methionine sources. In conclusion, methionine intake was positively associated with diabetes independent of food source, and it was modified by urbanization levels.This study was funded by the Natural Scientific Foundation in Qinghai Province (grant number: 2019-ZJ-932Q), and the National Key Research and Development Program of China (grant numbers: 2017YFC0907200 and 2017YFC0907201)

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

Complete Chloroplast Genome Sequence of a Major Invasive Species, Crofton Weed (Ageratina adenophora)

Crofton weed (Ageratina adenophora) is one of the most hazardous invasive plant species, which causes serious economic losses and environmental damages worldwide. However, the sequence resource and genome information of A. adenophora are rather limited, making phylogenetic identification and evolutionary studies very difficult. Here, we report the complete sequence of the A. adenophora chloroplast (cp) genome based on Illumina sequencing.The A. adenophora cp genome is 150, 689 bp in length including a small single-copy (SSC) region of 18, 358 bp and a large single-copy (LSC) region of 84, 815 bp separated by a pair of inverted repeats (IRs) of 23, 755 bp. The genome contains 130 unique genes and 18 duplicated in the IR regions, with the gene content and organization similar to other Asteraceae cp genomes. Comparative analysis identified five DNA regions (ndhD-ccsA, psbI-trnS, ndhF-ycf1, ndhI-ndhG and atpA-trnR) containing parsimony-informative characters higher than 2%, which may be potential informative markers for barcoding and phylogenetic analysis. Repeat structure, codon usage and contraction of the IR were also investigated to reveal the pattern of evolution. Phylogenetic analysis demonstrated a sister relationship between A. adenophora and Guizotia abyssinica and supported a monophyly of the Asterales.We have assembled and analyzed the chloroplast genome of A. adenophora in this study, which was the first sequenced plastome in the Eupatorieae tribe. The complete chloroplast genome information is useful for plant phylogenetic and evolutionary studies within this invasive species and also within the Asteraceae family

Clonal evolution in liver cancer at single-cell and single-variant resolution.

Genetic heterogeneity of tumor is closely related to its clonal evolution, phenotypic diversity and treatment resistance, and such heterogeneity has only been characterized at single-cell sub-chromosomal scale in liver cancer. Here we reconstructed the single-variant resolution clonal evolution in human liver cancer based on single-cell mutational profiles. The results indicated that key genetic events occurred early during tumorigenesis, and an early metastasis followed by independent evolution was observed in primary liver tumor and intrahepatic metastatic portal vein tumor thrombus. By parallel single-cell RNA-Seq, the transcriptomic phenotype of HCC was found to be related with genetic heterogeneity. For the first time we reconstructed the single-cell and single-variant clonal evolution in human liver cancer, and dissection of both genetic and phenotypic heterogeneity will facilitate better understanding of their relationship

Search for light dark matter from atmosphere in PandaX-4T

We report a search for light dark matter produced through the cascading decay of $\eta$ mesons, which are created as a result of inelastic collisions between cosmic rays and Earth's atmosphere. We introduce a new and general framework, publicly accessible, designed to address boosted dark matter specifically, with which a full and dedicated simulation including both elastic and quasi-elastic processes of Earth attenuation effect on the dark matter particles arriving at the detector is performed. In the PandaX-4T commissioning data of 0.63 tonne$\cdot$year exposure, no significant excess over background is observed. The first constraints on the interaction between light dark matter generated in the atmosphere and nucleus through a light scalar mediator are obtained. The lowest excluded cross-section is set at $5.9 \times 10^{-37}{\rm cm^2}$ for dark matter mass of $0.1$ MeV$/c^2$ and mediator mass of 300 MeV$/c^2$. The lowest upper limit of $\eta$ to dark matter decay branching ratio is $1.6 \times 10^{-7}$

Efficient radical-based light-emitting diodes with doublet emission.

Organic light-emitting diodes (OLEDs)1-5, quantum-dot-based LEDs6-10, perovskite-based LEDs11-13 and micro-LEDs14,15 have been championed to fabricate lightweight and flexible units for next-generation displays and active lighting. Although there are already some high-end commercial products based on OLEDs, costs must decrease whilst maintaining high operational efficiencies for the technology to realise wider impact.  Here we demonstrate efficient action of radical-based OLEDs16, whose emission originates from a spin doublet, rather than a singlet or triplet exciton. While the emission process is still spin-allowed in these OLEDs, the efficiency limitations imposed by triplet excitons are circumvented for doublets. Using a luminescent radical emitter, we demonstrate an OLED with maximum external quantum efficiency of 27 per cent at a wavelength of 710 nanometres-the highest reported value for deep-red and infrared LEDs. For a standard closed-shell organic semiconductor, holes and electrons occupy the highest occupied and lowest unoccupied molecular orbitals (HOMOs and LUMOs), respectively, and recombine to form singlet or triplet excitons. Radical emitters have a singly occupied molecular orbital (SOMO) in the ground state, giving an overall spin-1/2 doublet. If-as expected on energetic grounds-both electrons and holes occupy this SOMO level, recombination returns the system to the ground state, giving no light emission. However, in our very efficient OLEDs, we achieve selective hole injection into the HOMO and electron injection to the SOMO to form the fluorescent doublet excited state with near-unity internal quantum efficiency

BLOOM: A 176B-Parameter Open-Access Multilingual Language Model

Large language models (LLMs) have been shown to be able to perform new tasks based on a few demonstrations or natural language instructions. While these capabilities have led to widespread adoption, most LLMs are developed by resource-rich organizations and are frequently kept from the public. As a step towards democratizing this powerful technology, we present BLOOM, a 176B-parameter open-access language model designed and built thanks to a collaboration of hundreds of researchers. BLOOM is a decoder-only Transformer language model that was trained on the ROOTS corpus, a dataset comprising hundreds of sources in 46 natural and 13 programming languages (59 in total). We find that BLOOM achieves competitive performance on a wide variety of benchmarks, with stronger results after undergoing multitask prompted finetuning. To facilitate future research and applications using LLMs, we publicly release our models and code under the Responsible AI License