Background
Neuropathic pain is a debilitating disease caused by damage or diseases of the somatosensory nervous system. Previous research has indicated potential associations between neuropathic pain ...and aging. However, the mechanisms by which they are interconnected remain unclear. In this study, we aim to identify the common differentially expressed genes (co-DEGs) between neuropathic pain and aging through integrated bioinformatics methods and further explore the underlying molecular mechanisms.
Methods
The microarray datasets GSE24982, GSE63442, and GSE63651 were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and co-DEGs were first identified. Functional enrichment analyses, protein-protein Interaction (PPI) network, module construction and hub genes identification were performed. Immune infiltration analysis was conducted. Targeted transcription factors (TFs), microRNAs (miRNAs) and potential effective drug compounds for hub genes were also predicted.
Results
A total of 563 and 1,250 DEGs of neuropathic pain and aging were screened, respectively. 16 genes were further identified as co-DEGs. The functional analysis emphasizes the vital roles of the humoral immune response and complement and coagulation cascades in these two diseases. Cxcl14, Fblim1, RT1-Da, Serping1, Cfd, and Fcgr2b were identified as hub genes. Activated B cell, mast cell, activated dendritic cell, CD56 bright natural killer cell, effector memory CD8 + T cell, and type 2 T helper cell were significantly up-regulated in the pain and aging condition. Importantly, hub genes were found to correlate with the activated B cell, activated dendritic cell, Gamma delta T cell, central memory CD4 + T cell and mast cell in pain and aging diseases. Finally, Spic, miR-883-5p, and miR-363-5p et al. were predicted as the potential vital regulators for hub genes. Aldesleukin, Valziflocept, MGD-010, Cinryze, and Rhucin were the potential effective drugs in neuropathic pain and aging.
Conclusion
This study identified co-DEGs, revealed molecular mechanisms, demonstrated the immune microenvironment, and predicted the possible TFs, miRNAs regulation networks and new drug targets for neuropathic pain and aging, providing novel insights into further research.
A sequential Rh(III)-catalyzed C-H activation/annulation of
-hydroxybenzamides with propargylic acetates leading to the formation of NH-free isoquinolones is described. This reaction proceeds through ...a sequential C-H activation/alkyne insertion/intramolecular annulation/N-O bond cleavage procedure, affording a broad spectrum of products with diverse substituents in moderate-to-excellent yields. Notably, this protocol features the simultaneous formation of two new C-C/C-N bonds and one heterocycle in one pot with the release of water as the sole byproduct.
科学划分村庄类型并制定针对性的村庄发展策略是分类推进乡村振兴的基础。本研究以河南新县为例，分别采用综合指数法和障碍度模型测算村庄发展潜力，识别阻碍村庄发展的障碍因子类型和数量，并以此为基础进行村庄分类和分区，制定差异化的村庄发展策略。结果表明：新县村庄发展潜力存在明显的地域分异，呈现南北部和县城周边较高、东西部较低的总体空间格局，坡度、地质条件、人口和村庄用地规模、距县城和卫生院距离等是限制新县村庄发展的主要障碍因子，其中东南部的田铺乡和西南部的卡房乡个别村庄障碍因子数较多，未来继续保留发展的难度较大。新县全域村庄划分为特色保护类23个、城郊融合类9个、集聚提升类79个、搬迁撤并类13个、整治改善类69个，占比分别为11.92%、4.66%、40.93%、6.74%、35.75%，并采用SKATER空间聚类算法划分村庄发展分区，在此基础上依据各分区村庄发展特征、优势和短板提出针对性村庄发展策略。本研究可为村庄发展障碍因子识别及乡村振兴精准施策等相关研究和实践提供借鉴。Scientific classification of village types and formulation of village development strategies are the prerequisites for promoting category-wise rural revitalization. Based on the evaluation of village development capacity in Xinxian County, Henan Province, China, this study introduces an obstacle degree model, which identified the types and numbers of factors that hinder the development of each village. Based on the development capacity and obstacle degree, this study classified and zoned the villages to implement targeted policies. The results showed that： the development capac
Three novel phosphorescent host materials, 4′,4‴-(4-phenylpyridine-2,6-diyl)bis(
N
,
N
-diphenyl-1,1′-biphenyl-4-amine)
(P1),
2,6-bis(4′-(naphthalen-1-yl)-1,1′-biphenyl-4-yl)-4-phenylpyridine
(P2)
, ...and 2,6-bis(3′,5′-dimethyl-1,1′-biphenyl-4-yl)-4-phenylpyridine
(P3)
, based on triphenylpyridine with a symmetrical molecular conformation were designed and synthesized from 2,6-bis(4-bromophenyl)-4-phenylpyridine
(3)
reacting with 4-(diphenylamino)phenylboronic acid
(A1)
, 4-(naphthalen-1-yl)phenylboronic acid
(A2)
, and (3,5-dimethylphenyl)boronic acid
(A3)
through Suzuki coupling reaction, respectively. The compounds obtained were characterized by elemental analysis,
1
H NMR, and
13
C NMR spectroscopy. The thermal properties of these materials were studied by thermogravimetric analysis and differential scanning calorimetry measurements, which showed that they exhibited excellent thermal stability with glass transition temperatures over 94 °C. Their photophysical properties were also investigated, and the results indicated that all compounds possessed considerably high triplet energy level greater than 2.6 eV; they also emitted blue fluorescence in different solvents. Finally, the results of the density function theory calculations revealed that the compound
P1
showed the well-separated frontier molecular orbital, which indicated that it possessed bipolar carrier transport ability for holes and electrons, whereas the compound
P2
and
P3
exhibited greater overlap between the highest occupied molecular orbital and the lowest unoccupied molecular orbital.
China has entered a new era of comprehensive promotion of rural revitalization and integrated urban–rural development. The identification and optimization of the spatial structure of urban and rural ...settlements are of great significance to the realization of rural revitalization and integrated urban–rural development. This study proposes a method framework for identifying and optimizing the spatial structure of urban and rural settlements from a hierarchical network perspective. This framework includes three parts—namely, the identification, analysis, and optimization of the hierarchical network structure of these settlements. The identification of this structure is the foundation of this study. To realize the identification, for each settlement, this study finds and retains its strongest interaction with other settlements which have a stronger capacity for development. This study used Hua County in Henan, China, as an example to verify the method framework. Results showed that the spatial structure of the urban and rural settlements in Hua County identified in this study was complete and continuous, with significant hierarchical and community characteristics. Based on this, a five-level optimization system of these settlements was constructed. This study expands the method used to study the spatial structure of urban and rural settlements from the network perspective and has a theoretical and practical significance for the optimization of the spatial structure of these settlements.
Giardia spp. are flagellated protozoan parasites that infect humans and many other vertebrates worldwide. Currently seven species of Giardia are considered valid.
Here, we report a new species, ...Giardia cricetidarum n. sp. in hamsters. Trophozoites of G. cricetidarum n. sp. are pear-shaped with four pairs of flagella and measure on average 14 μm (range 12-18 μm) in length and 10 μm (range 8-12 μm) in width. The trophozoites of the new species are generally larger and stouter than those of most of the other Giardia spp. and exhibit the lowest length/width ratio (c.1.40) of all recognized Giardia species. Cysts of G. cricetidarum n. sp. are ovoid and measure on average 11 μm (range 9-12 μm) in length and 10 μm (range 8-10 μm) in width and are indistinguishable from the cysts of other Giardia species. Molecular phylogenetic analyses based on beta-giardin, small subunit rRNA, and elongation factor-1 alpha loci all demonstrated that G. cricetidarum n. sp. is genetically distinct from all currently accepted Giardia spp. Investigation of the host range indicated that the new species was only found in hamsters (including Phodopus sungorus, P. campbelli and Mesocricetus auratus), while all the other described mammal-parasitizing species (G. muris, G. microti and G. intestinalis) each infect multiple hosts. Cross-transmission studies further demonstrated the apparent host specificity of G. cricetidarum n. sp. as it only infected hamsters. Trophozoites were found in high numbers in hamster intestines (5 × 10
- 5 × 10
) and was rarely detected co-infecting with other Giardia spp. in the common hamster, suggesting it has some advantages in parasitizing hamsters.
This study has identified a new species of Giardia, which appears to be specific to hamsters, and together with the three other mammal-parasitizing Giardia species with different host ranges, may be able to be used as a model system for the study of evolutionary divergence of host parasitism strategies in Giardia.
Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and severe side effect of first-line chemotherapeutic agents. The association between circular RNAs (circRNAs) and CIPN remains ...unclear. In this study, CIPN models were constructed with Taxol, while 134 differentially expressed circRNAs, 353 differentially expressed long non-coding RNAs, and 86 differentially expressed messenger RNAs (mRNAs) were identified utilizing RNA sequencing. CircRNA-targeted microRNAs (miRNAs) were predicted using miRanda, and miRNA-targeted mRNAs were predicted using TargetScan and miRDB. The intersection of sequencing and mRNA prediction results was selected to establish the circRNA–miRNA–mRNA networks, which include 15 circRNAs, 18 miRNAs, and 11 mRNAs. Functional enrichment pathway analyses and immune infiltration analyses revealed that differentially expressed mRNAs were enriched in the immune system, especially in T cells, monocytes, and macrophages. Cdh1, Satb2, Fas, P2ry2, and Zfhx2 were further identified as hub genes and validated by RT-qPCR, correlating with macrophages, plasmacytoid dendritic cells, and central memory CD4 T cells in CIPN. Additionally, we predicted the associated diseases, 36 potential transcription factors (TFs), and 30 putative drugs for hub genes using the DisGeNET, TRRUST, and DGIdb databases, respectively. Our results indicated the crucial role of circRNAs, and the immune microenvironment played in CIPN, providing novel insights for further research.
Astringency has an important impact on the taste quality of tea infusion, a process which occurs when polyphenols complex with salivary proteins to form an impermeable membrane. (-)-Epigallocatechin ...gallate (EGCG) is the main astringent compound found in green tea and mucin is the main protein present in saliva. Determining the turbidity of EGCG-mucin mixtures is an effective method to quantify the astringency intensity of EGCG solutions. In this study, the effects of taste-related, substances present during green tea infusion, on the turbidity of EGCG-mucin mixtures was investigated under the reacting conditions of a pH value of 5.0, at 37 °C, and for 30 min. The results showed that epicatechins, caffeic acid, chlorogenic acid, and gallic acid reduced the turbidity of EGCG-mucin mixtures, while rutin increased turbidity. Metal ions increased the turbidity of EGCG-mucin mixtures. These can be arranged by effectiveness as Al
> K
> Mg
> Ca
. Caffeine, theanine, and sodium glutamate all decreased the turbidity values of EGCG-mucin mixtures, but sucrose had a weak effect. Further experiments confirmed that the turbidity of green tea infusion-mucin mixture indicated the astringent intensity of green tea infusion, and that the turbidity was significantly correlated with the contents of tea polyphenols and EGCG.
Background
Long noncoding RNA (lncRNA) in plasma exosomes is a potential non-invasive diagnostic biomarker for diabetic retinopathy (DR). However, the changes in plasma exosomal lncRNAs and ...diagnostic relevance in patients with DR patients remain unclear.
Methods
A case–control study with type 2 diabetes mellitus (T2DM) and patients with comorbid DR were enrolled, and their clinical information and blood samples were collected. Plasma exosomes were extracted, and the relative expression levels of representative differentially expressed exosomal lncRNAs were determined. A logistic regression model was used to analyze the relationships of DR with relative lncRNA expression and DR-related factors, and receiver operating characteristic (ROC) curve analysis was used to evaluate the value of exosomal lncRNAs for DR diagnosis.
Results
Sixty-two patients with T2DM and sixty-two patients with DR were matched by age, sex, and disease duration. The fasting blood glucose concentration, glycosylated hemoglobin level (HbA
1c
), and relative expression of the plasma exosomal lncRNA
DLX6-AS1
were significantly higher in the DR group than in the T2DM group, whereas the 2-h C-peptide concentration and relative expression of the lncRNAs
PRINS
and
FAM190A-3
were lower in the DR group. After adjusting for relevant confounders, the fasting blood glucose concentration, HbA
1c
level, 2-h C-peptide concentration, and relative expression of lncRNA
DLX6-AS1
,
PRINS
, and
FAM190A-3
were found to be associated with DR. Both
DLX6-AS1
area under the curve (AUC): 0.658 (0.562–0.754),
PRINS
AUC: 0.798 (0.722–0.873), and
FAM190A-3
AUC: 0.603 (0.503-0.702) expression had predictive value for DR diagnosis. The combination of
DLX6-AS1
and
PRINS
yielded an AUC of 0.813 (0.740–0.886). In males, the combination of
DLX6-AS1
and
PRINS
yielded an AUC of 0.860 (0.780–0.940).
Conclusion
The fasting blood glucose concentration, HbA
1c
level, and exosomal
DLX6-AS1
expression were identified as risk factors for DR, whereas the 2-h C-peptide concentration and exosomal
PRINS
and
FAM190A-3
were identified as protective against DR. The combination of exosomal
DLX6-AS1
and
PRINS
had good diagnostic value for DR in the general population and males. More attention should be paid to the role of exosomal
PRINS
expression as a predictive and diagnostic DR biomarker in females.
Toxin-like proteins and peptides of skin secretions from amphibians play important physiological and pathological roles in amphibians. βγ-CAT is a Chinese red-belly toad-derived pore-forming ...toxin-like protein complex that consists of aerolysin domain, crystalline domain, and trefoil factor domain and induces various toxic effects via its membrane perforation process, including membrane binding, oligomerization, and endocytosis. Here, we observed the death of mouse hippocampal neuronal cells induced by βγ-CAT at a concentration of 5 nM. Subsequent studies showed that the death of hippocampal neuronal cells was accompanied by the activation of Gasdermin E and caspase-1, suggesting that βγ-CAT induces the pyroptosis of hippocampal neuronal cells. Further molecular mechanism studies revealed that the pyroptosis induced by βγ-CAT is dependent on the oligomerization and endocytosis of βγ-CAT. It is well known that the damage of hippocampal neuronal cells leads to the cognitive attenuation of animals. The impaired cognitive ability of mice was observed after intraperitoneal injection with 10 μg/kg βγ-CAT in a water maze assay. Taken together, these findings reveal a previously unknown toxicological function of a vertebrate-derived pore-forming toxin-like protein in the nerve system, which triggers the pyroptosis of hippocampal neuronal cells, ultimately leading to hippocampal cognitive attenuation.
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