CD4+ T-Cell Senescence in Neurodegenerative Disease: Pathogenesis and Potential Therapeutic Targets.

With the increasing proportion of the aging population, neurodegenerative diseases have become one of the major health issues in society. Neurodegenerative diseases (NDs), including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are characterized by progressive neurodegeneration associated with aging, leading to a gradual decline in cognitive, emotional, and motor functions in patients. The process of aging is a normal physiological process in human life and is accompanied by the aging of the immune system, which is known as immunosenescence. T-cells are an important part of the immune system, and their senescence is the main feature of immunosenescence. The appearance of senescent T-cells has been shown to potentially lead to chronic inflammation and tissue damage, with some studies indicating a direct link between T-cell senescence, inflammation, and neuronal damage. The role of these subsets with different functions in NDs is still under debate. A growing body of evidence suggests that in people with a ND, there is a prevalence of CD4+ T-cell subsets exhibiting characteristics that are linked to senescence. This underscores the significance of CD4+ T-cells in NDs. In this review, we summarize the classification and function of CD4+ T-cell subpopulations, the characteristics of CD4+ T-cell senescence, the potential roles of these cells in animal models and human studies of NDs, and therapeutic strategies targeting CD4+ T-cell senescence.

Natural variations of HvSRN1 modulate the spike rachis node number in barley.

Grain number, one of the major determinants of yield in Triticeae crops, is largely determined by spikelet number and spike rachis node number (SRN). Here, we identified three quantitative trait loci (QTLs) for SRN using 145 recombinant inbred lines derived from a barley R90/1815D cross. qSRN1, the major-effect QTL, was mapped to chromosome 2H and explained up to 38.77% of SRN variation. Map-based cloning revealed that qSRN1 encodes the RAWUL domain-containing protein HvSRN1. Further analysis revealed that two key SNPs in the HvSRN1 promoter region (∼2 kb upstream of the transcription start site) affect the transcript level of HvSRN1 and contribute to variation in SRN. Similar to its orthologous proteins OsLAX2 and ZmBA2, HvSRN1 showed protein-protein interactions with HvLAX1, suggesting that the LAX2-LAX1 model for spike morphology regulation may be conserved in Poaceae crops. CRISPR-Cas9-induced HvSRN1 mutants showed reduced SRN but increased grain size and weight, demonstrating a trade-off effect. Our results shed light on the role of HvSRN1 variation in regulating the balance between grain number and weight in barley.

DNA barcoding identification of grafted Semen Ziziphi Spinosae and transcriptome study of wild Semen Ziziphi Spinosae.

Semen Ziziphi Spinosae (SZS) is the dried and ripe seeds of Ziziphus jujuba var. spinosa. Currently, the yield of naturally grown SZS is unstable owing to environmental factors. Grafting high-quality sour jujube scions onto sour jujube or jujube tree stocks can result in a greater yield. However, the effects of grafting on the quality and gene expression of SZS have rarely been reported. This study used a DNA barcoding technique, high-performance liquid phase-evaporative luminescence detector (HPLC-ELSD), and transcriptomics to investigate the origin and genetic differences between grafted and wild jujube seeds. DNA barcoding identified all samples as Ziziphus jujuba var. spinosa. HPLC-ELSD analysis revealed a higher content of grafted SZS compared to that of the wild SZS. Transcriptome analysis of the metabolic pathways in SZS showed that 22 and 19 differentially expressed gene sequences encoded enzymes related to flavonoids and saponin synthesis, respectively. Weighted correlation network analysis (WGCNA) identified 15 core genes governing the differences in medicinal components between grafted and wild SZS. This study demonstrated the use of DNA barcoding and fingerprint methods to identify jujube seed species and effectively capture ingredient information of medicinal materials. Additionally, transcriptome technology provided data for identifying core differential genes, facilitating studies on quality differences between grafted and wild SZS.

In situ detection and mass spectrometry imaging of protein-related metabolites in Bombyx batryticatus before and after frying with wheat bran.

Bombyx batryticatus is derived from the dried larva of Bombyx mori Linnaeus infected by Beauveria bassiana (Bals.) Vuillant. Raw Bombyx batryticatus should be stir-fried before oral administration due to its irritation to the gastrointestinal tract. Nevertheless, it is still an arduous task to uncover the intrinsic mechanism of Bombyx batryticatus processing. In this study, we collected two types of Bombyx batryticatus, one being stir-fried and the other serving as a control. Then, an informative approach, which integrated matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) with chemometrics analysis, was established to screen processing-associated markers and reveal in situ spatial distribution patterns of protein-related metabolites. After optimization of experimental conditions, 21 ions were initially detected from Bombyx batryticatus, including amino acids and peptides. In addition, 15 differential markers were screened by orthogonal projection to potential structure discriminant analysis (OPLS-DA), which were localized and visualized in the transverse section of Bombyx batryticatus by MSI. Eventually, it can be demonstrated that the stir-frying process reduces toxicity while potentially boosting specific biological activities of Bombyx batryticatus. In summary, the established strategy could not only clarify the chemical transformation of protein-related metabolites from Bombyx batryticatus before and after frying with wheat bran, but also reveal the significance of Chinese medicine processing technology.

Background construction for tracing metal inputs in estuarine sediments of the Liaodong Bay (NE China): Linear-regression method.

Intertidal sediments are a significant reservoir of trace metals originating from human activities and natural weathering. However, the absence of geochemical background levels and the heterogeneity of sediment components are challenging to quantify the extent of trace metal contamination. For distinguishing the contribution of natural and anthropogenic inputs, dynamic background functions were established by linear regressions of trace metals (i.e., Zn, Cr, Ni, Cu, Cd, and Pb) against normalizer Al in three cores of the Daliao River estuary. Lead-210 geochronology indicated that trace metals have accumulated rapidly in the sediments since 1985 CE. The calculation results of enrichment factors and excess fluxes confirmed that the increased contents of Zn and Cd were contaminated by human activities. Conversely, the increased contents of others (i.e., Cr, Ni, Cu, and Pb) were attributed to variations in geological background levels, driven by the combination of grain size and organic matter. Overall levels of trace metals were at medium-low ecological risks (MSQG-Q: 0.19-0.38), and Ni at high-medium ecological risks (PEL-QNi > 0.5) in recent decades. Interestingly, these Ni probably originated from natural weathering rather than anthropogenic inputs because sediment quality guidelines lacked consideration for the differences in regional background levels and grain size. This procedure could provide the fundamental framework for regional investigations of spatial and temporal contamination, applied to other similar intertidal zones of sediment quality management.

A conserved type III effector RipB is recognized in tobacco and contributes to Ralstonia solanacearum virulence in susceptible host plants.

Ralstonia solanacearum, the causal agent of bacterial wilt, causes devastating diseases in a wide range of plants including potato, tomato, pepper and tobacco. The pathogen delivers approximately 70 type III effectors (T3Es) into plant cells during infection. In this study, we confirmed that a T3E RipB is recognized in tobacco. We further demonstrated that RipB is conserved among R. solanacearum isolates and five different ripB alleles are all recognized in tobacco. The ripB from GMI1000 was transformed into susceptible host Arabidopsis, and a defect in root development was observed in ripB-transgenic plants. Pathogen inoculation assays showed that ripB expression promoted plant susceptibility to R. solanacearum infection, indicating that RipB contributes to pathogen virulence in Arabidopsis. Expression of ripB in roq1 mutant partially suppressed reactive oxygen species production, confirming that RipB interferes with plant basal defense. Interestingly, ripB expression promoted cytokinin-related gene expression in Arabidopsis, suggesting a role of cytokinin signaling pathway in plant-R. solanacearum interactions. Finally, RipB harbors potential 14-3-3 binding motifs, but the associations between RipB and 14-3-3 proteins were undetectable in yeast two-hybrid assay. Together, our results demonstrate that multiple ripB alleles are recognized in Nicotiana, and RipB suppresses basal defense in susceptible host to promote R. solanacearum infection.

Revisiting the structure of arabinogalactan from Lycium barbarum and the impact of its side chain on anti-ageing activity.

In this study, we obtained all the homogeneous LBGP70 (arabinogalactan-protein complex), LBGP70-OL (sugar chain of LBGP70), and LBGP70-OL-I (backbone part of LBGP70-OL) fraction from crude Lycium barbarum polysaccharides (LBP) by stepwise precipitation. The structural features of LBGP70-OL were investigated by a series of analytical techniques and chemical methods, which was identified as a highly branched polysaccharide with an average of 9 branches per 10 sugar backbone units. The backbone was only →6)-ß-Galp-(1→ residues, substituted at the C3 position. The side chains contained ß-Galp-(1→, α-Araf-(1→, α-Araf-(1 â†’ 3)-ß-Araf-(1 â†’ 3)-ß-Araf-(1→, α-Araf-(1 â†’ 3)-ß-Gap-(1 â†’ 3)-ß-Galp-(1→, α-Araf-(1 â†’ [5)-ß-Araf-(1]4 â†’ 3)-ß-Galp-(1→. LBGP70-OL had the highest anti-ageing activity, with its side chain and backbone exhibiting a synergistic effect. LBGP70-OL exerted the anti-ageing activity by attenuating SA-ß-Gal activity, preventing cell cycle arrest, increasing antioxidant enzyme activity, protecting the cell membranes from oxidative damage, and regulating the senescence-related genes Sirt1, NAMPT, and Prx1. These results lay the fundamental for further studies on the structure-function relationships of LBP.

A BTB/POZ domain-containing protein negatively regulates plant immunity in Nicotiana benthamiana.

Plants have evolved immune systems to fight against pathogens. However, it is still largely unknown how the plant immunity is finely regulated. Here we identified a BTB/POZ domain-containing protein, namely NbBTB, which is predicted to be a member of the ubiquitin E3 ligase complex. The NbBTB expression is downregulated upon the oomycete pathogen Phytophthora parasitica infection. Overexpression of NbBTB in Nicotiana benthamiana promoted plant susceptibility to P. parasitica infection, and silencing NbBTB increased plant resistance to P. parasitica, indicating that NbBTB negatively modulates plant basal defense. Interestingly, overexpressing or silencing NbBTB did not affect plant resistance to two bacterial pathogens Ralstonia solanacearum and Pseudomonas syringae, suggesting that NbBTB is specifically involved in basal defense against oomycete pathogen. Expression of NbBTB suppressed hypersensitive response (HR) triggered by avirulence proteins from both R. sonanacearum and P. infestans, and silencing NbBTB showed the opposite effect, indicating that NbBTB negatively regulates effector-triggered immunity (ETI). Protein accumulation of avirulence effectors in NbBTB-silenced plants was significantly enhanced, suggesting that NbBTB is likely to negatively modulate ETI by affecting effector protein accumulation. Together, our results demonstrated that NbBTB is a negative regulator in both plant basal defense and ETI.

Distribution and pollution assessment of heavy metals in the intertidal zone environments of typical sea areas in China.

The heavy metals (Cu, Cr, Zn, Cd, Pb) were analysed for 217 surface sediment samples collected across 14 typical intertidal zone areas in China. The data reveals the heavy metals spatial distribution patterns and correlations among their concentrations. Cu, Zn, Cd and Cr showed similar trends of spatial variation and the correlations between the concentrations of every two heavy metals were significantly positive except for the correlation between Pb and Cr concentrations. By using Nemerow index method, Enrichment factor and Sediment Quality Guidelines, it is found that Hangzhou Bay and Jiulong River Estuary were polluted, Yingluo Bay and Dongzhaigang Bay were Cd-rich areas. Except Beidaihe shoal, Sishili Bay and Yingluo Bay that were not exposed to any ecological risk of heavy metals and had no adverse biotoxic effects, the other 11 typical intertidal zone areas were exposed to moderate ecological risk of heavy metals in the sediment with potential adverse biotoxic effects.

Distribution and sources of polycyclic aromatic hydrocarbons in surface sediments from the Bering Sea and western Arctic Ocean.

To analyze the distribution and sources of polycyclic aromatic hydrocarbons (PAHs) and evaluate their potential ecological risks, the concentrations of 16 PAHs were measured in 43 surface sediment samples from the Bering Sea and western Arctic Ocean. Total PAH (tPAH) concentrations ranged from 36.95 to 150.21 ng/g (dry weight). In descending order, the surface sediment tPAH concentrations were as follows: Canada Basin>northern Chukchi Sea>Chukchi Basin>southern Chukchi Sea>Aleutian Basin>Makarov Basin>Bering Sea shelf. The Bering Sea and western Arctic Ocean mainly received PAHs of pyrogenic origin due to pollution caused by the incomplete combustion of fossil fuels. The concentrations of PAHs in the sediments of the study areas did not exceed effects range low (ERL) values.

Spatial distribution and historical trends of heavy metals in the sediments of petroleum producing regions of the Beibu Gulf, China.

The concentrations of As, Sb, Hg, Pb, Cd, and Ba in the surface and core sediments of the oil and gas producing region of the Beibu Gulf were measured by Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES), Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and Atomic Fluorescence Spectrometry (AFS), and the spatial distribution and historical trends of these elements are discussed. The results show that the concentrations of these elements are highest near the platforms. The results of Enrichment Factor (EF) and Potential Ecological Risk Index (PERI) also reveal significantly higher enrichment around the platforms, which imply that the offshore petroleum production was the cause of the unusual distribution and severe enrichment of these elements in the study area. The environment around the platforms was highly laden with toxic elements, thereby representing a very high ecological risk to the environment of the study area.

The complete mitochondrial genome of Neobenedenia melleni (Platyhelminthes: Monogenea): mitochondrial gene content, arrangement and composition compared with two Benedenia species.

The complete mitochondrial (mt) genome sequences of Neobenedenia melleni were determined and compared with those of Benedenia seriolae and B. hoshinai. This circular genome comprises 13,270 bp and includes all 36 typical mt genes found in flatworms. Total AT content of N. melleni is 75.9 %. ATG is the most common start codon, while nad4L is initiated by GTG. All protein-coding genes are predicted to terminate with TAG and TAA. N. melleni has the trnR with a TCG anticodon, which is the same to B. seriolae but different from B. hoshinai (ACG). The mt gene arrangement of N. melleni is similar to that of B. seriolae and B. hoshinai with the exception of three translocations (trnF, trnT and trnG). The overlapped region between nad4L and nad4 was found in the N. melleni mt genome, which was also reported for the published Gyrodactylus species, but it was not found in those of B. seriolae and B. hoshinai, which are non-coding regions instead. The present study provides useful molecular characters for species or strain identification and systematic studies of this parasite.