Identification of disease-specific genes related to immune infiltration in nonalcoholic steatohepatitis using machine learning algorithms.

To identify disease signature genes associated with immune infiltration in nonalcoholic steatohepatitis (NASH), we downloaded 2 publicly available gene expression profiles, GSE164760 and GSE37031, from the gene expression omnibus database. These profiles represent human NASH and control samples and were used for differential genes (DEGs) expression screening. Two machine learning methods, the Least Absolute Shrinkage and Selection Operator regression model and Support Vector Machine Recursive Feature Elimination, were used to identify candidate disease signature genes. The CIBERSORT deconvolution algorithm was employed to analyze the infiltration of 22 immune cell types in NASH. Additionally, we constructed a NASH cell model using HepG2 cells treated with oleic acid and free fatty acids. The construction of the cell model was verified using oil red O staining, and Western blotting was used to detect the protein expression of the disease signature genes in both control and model groups. As a result, a total of 262 DEGs were identified. These DEGs were primarily associated with metal ion transmembrane transporter activity, sodium ion transmembrane transporter protein activity, calcium ion, and neuroactive ligand-receptor interactions. FOS, IGFBP2, dual-specificity phosphatase 1 (DUSP1), and IKZF3 were identified as disease signature genes of NASH by the least absolute shrinkage and selection operator and Support Vector Machine Recursive Feature Elimination algorithms for DEGs analysis. The receiver operating characteristic curves showed that FOS, IGFBP2, DUSP1, and IKZF3 had good diagnostic value (area under receiver operating characteristic curve > 0.8). These findings were validated in the GSE89632 dataset and through cellular assays. Immunocyte infiltration analysis revealed that NASH was associated with CD8 T cells, CD4 T cells, follicular helper T cells, resting NK cells, eosinophils, regulatory T cells, and γδ T cells. The FOS, IGFBP2, DUSP1, and IKZF3 genes were specifically associated with follicular helper T cells. Lipid droplet aggregation significantly increased in HepG2 cells treated with oleic acid and free fatty acids, indicating successful construction of the cell model. In this model, the expression of FOS, IGFBP2, and DUSP1 was significantly decreased, while that of IKZF3 was significantly elevated (P < .01, P < .001) compared with the control group. Therefore, FOS, IGFBP2, DUSP1, and IKZF3 can be considered as disease signature genes associated with immune infiltration in NASH.

Acute acquired concomitant esotropia with congenital paralytic strabismus: A case report.

BACKGROUND: An unusual case of acute acquired concomitant esotropia (AACE) with congenital paralytic strabismus in the right eye is reported. CASE SUMMARY: A 23-year-old woman presented with complaints of binocular diplopia and esotropia of the right eye lasting 4 years and head tilt to the left since 1 year after birth. The Bielschowsky head tilt test showed right hypertropia on a right head tilt. She did not report any other intracranial pathology. A diagnosis of AACE and right congenital paralytic strabismus was made. Then, she underwent medial rectus muscle recession and lateral rectus muscle resection combined with inferior oblique muscle myectomy in the right eye. One day after surgery, the patient reported that she had no diplopia at either distance or near fixation and was found to be orthophoric in the primary position; furthermore, her head posture immediately and markedly improved. CONCLUSION: In future clinical work, in cases of AACE combined with other types of strabismus, we can perform conventional single surgery for both at the same time, and the two types of strabismus can be solved simultaneously.

Single-cell RNA sequencing reveals new subtypes of lens superficial tissue in humans.

Although the cell atlas of the human ocular anterior segment of the human eye was revealed by single-nucleus RNA sequencing, whether subtypes of lens stem/progenitor cells exist among epithelial cells and the molecular characteristics of cell differentiation of the human lens remain unclear. Single-cell RNA sequencing is a powerful tool to analyse the heterogeneity of tissues at the single cell level, leading to a better understanding of the processes of cell differentiation. By profiling 18,596 cells in human lens superficial tissue through single-cell sequencing, we identified two subtypes of lens epithelial cells that specifically expressed C8orf4 and ADAMTSL4 with distinct spatial localization, a new type of fibre cells located directly adjacent to the epithelium, and a subpopulation of ADAMTSL4+ cells that might be lens epithelial stem/progenitor cells. We also found two trajectories of lens epithelial cell differentiation and changes of some important genes during differentiation.

Study on Fluorescence Recognition of Fe3+, Cr2O72- and p-Nitrophenol by a Cadmium Complex and Related Mechanism.

The effective detection of environmental pollutants is very important to the sustainable development of human health and the environment. A luminescent Cd(II) coordination complex, {[Cd(dbtdb)(1,2,4-H3btc)]·0.5H2O}n (1) (dbtdb = 1-(2,3,5,6-tetramethyl-4-((2-(thiazol-4-yl)-2H-benzo[d]imidazol-3(3aH)-yl)methyl)benzyl)-2,7a-dihydro-2-(thiazol-4-yl)-1H-benzo[d]imidazole, 1,2,4-H3btc = 1,2,4-benzenetricarboxylic acid), was obtained by hydrothermal reactions. Complex 1 has a chain structure decorated with uncoordinated Lewis basic O and S donors and provides good sensing of Fe3+, Cr2O72-, and p-nitrophenol with fluorescence quenching through an energy transfer process. The calculated binding constants were 3.3 × 103 mol-1 for Fe3+, 2.36 × 104 mol-1 for Cr2O72-, and 9.3 × 103 mol-1 for p-nitrophenol, respectively. These results show that 1 is a rare multiresponsive sensory material for efficient detection of Fe3+, Cr2O72-, and p-nitrophenol.

Lenalidomide attenuates IMQ-induced inflammation in a mouse model of psoriasis.

Psoriasis is a type of chronic autoimmune-mediated inflammatory skin condition in which clinical manifestations are characterized by erythema and scaly changes, with complex pathogenesis and ease of relapse, and it is difficult to cure. Lenalidomide (Len) is a structural analog of thalidomide, which belongs to the second generation of immunomodulators and has the functions of tumor killing, immune regulation, anti-angiogenesis and regulation of the myeloma microenvironment. In the current experiment, we investigated the therapeutic effect of transdermal application of Len on the pathological changes of imiquimod (IMQ)-induced skin irritations and inflammation in psoriatic-like mice. The in vivo results revealed that Len nanoemulsion-based gels markedly reduced the IMQ-induced Psoriasis Area Severity Index (PASI) score, spleen-to-body weight index and CD4 protein expression in the derma of mice and improved IMQ-induced skin inflammatory cell infiltration. Transcriptome sequencing was intended to obtain the differentially expressed genes among the skin of Con mice and the skin of IMQ mice, and then, the GO enrichment classification and KEGG pathway analysis of the significant genes was executed to obtain major signaling pathways in the pathogenesis of the psoriasis mouse model. It was found that the PI3K/AKT signaling pathway was a major pathway in the pathogenesis of psoriasis in a mouse model induced by IMQ. The immunohistochemical results confirmed that Len could modulate the protein expression of AKT and NF-κB in skin. In conclusion, the protective effect of transdermal administration of Len may be related to the inhibition of the PI3K/AKT signaling pathway and its downstream NF-κB pathway against IMQ-induced psoriasis in mice.

Molecular mechanism of benzo [a] pyrene regulating lipid metabolism via aryl hydrocarbon receptor.

BACKGROUND: Benzo [a] pyrene (BaP), a potent carcinogen, has been proved that it has toxicological effects via activation the aryl hydrocarbon receptor (AhR) pathway. AhR can participate in regulating lipogenesis and lipolysis. This topic will verify whether BaP regulates lipid metabolism via AhR. METHODS: (1) C57BL/6 mice were gavaged with BaP for 12 weeks to detect serum lipids, glucose tolerance, and insulin resistance. Morphological changes in white adipose tissue (WAT) were detected by Hematoxylin and Eosin staining. The mRNA expression levels of adipogenesis-related factors included recombinant human CCAAT/enhancer binding protein alpha (C/EBPα), peroxisome proliferator-activated receptor gamma (PPARγ), and fatty acid binding protein 4 (FABP4) and inflammatory factors included nuclear factor kappa-B (NF-κB), monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor alpha (TNF-α) were detected using PCR. (2) Neutral lipid content changes in differentiated 3 T3-L1 adipocytes treated with BaP with and w/o AhR inhibitor were detected by Oil red staining. The protein expression levels of adipogenesis- and decomposition-related factors included PPARγ coactivator-1 alpha (PGC-1α), and peroxisome proliferation-activated receptor alpha (PPARα) were detected using western blotting. The mRNA expression levels of inflammatory factors were detected using PCR. RESULTS: (1) BaP inhibited body weight gain, decreased lipid content, increased lipid levels, and decreased glucose tolerance and insulin tolerance in mice; (2) BaP reduced the expressions of C/EBPα, PPARγ, FABP4, PGC-1α, and PPARα and increased the expressions of NF-κB, MCP-1, and TNF-α by activating AhR. CONCLUSION: BaP inhibit fat synthesis and oxidation while inducing inflammation by activating AhR, leading to WAT dysfunction and causing metabolic complications.

Highly Selective Tandem Electroreduction of CO2 to Ethylene over Atomically Isolated Nickel-Nitrogen Site/Copper Nanoparticle Catalysts.

Herein, an effective tandem catalysis strategy is developed to improve the selectivity of the CO2 RR towards C2 H4 by multiple distinct catalytic sites in local vicinity. An earth-abundant elements-based tandem electrocatalyst PTF(Ni)/Cu is constructed by uniformly dispersing Cu nanoparticles (NPs) on the porphyrinic triazine framework anchored with atomically isolated nickel-nitrogen sites (PTF(Ni)) for the enhanced CO2 RR to produce C2 H4 . The Faradaic efficiency of C2 H4 reaches 57.3 % at -1.1 V versus the reversible hydrogen electrode (RHE), which is about 6 times higher than the non-tandem catalyst PTF/Cu, which produces CH4 as the major carbon product. The operando infrared spectroscopy and theoretic density functional theory (DFT) calculations reveal that the local high concentration of CO generated by PTF(Ni) sites can facilitate the C-C coupling to form C2 H4 on the nearby Cu NP sites. The work offers an effective avenue to design electrocatalysts for the highly selective CO2 RR to produce multicarbon products via a tandem route.

Comparison of larval performance and oviposition preference of Spodoptera frugiperda among three host plants: Potential risks to potato and tobacco crops.

Fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith), is a major polyphagous pest with the potential to seriously damage various crops. A better understanding of FAW's performance on different hosts may help to predict which plants will be attacked when the preferred host is absent, and facilitate the development of effective pest management practices. We compared the larval performance of FAW fed on maize with that of FAW fed on potato and tobacco, which are important crops in China, using an age-stage two-sex life table and adult female oviposition preference experiments. In cage experiments with potato, tobacco, or maize as the host, FAW reared on maize exhibited the strongest performance with shorter developmental time in the larval stage, longer longevity, and a higher reproductive rate in adults. Females oviposited on maize in preference to potato or tobacco. Compared with larvae fed on maize, those fed on potato and tobacco exhibited significantly lower survival, with only 31.61% and 8.13% developing to the adult stage, respectively. Several life table parameters, including the mean generation time (T), net reproductive rate (R0 ), finite rate of increase (λ), and intrinsic rate of natural increase (r) were negatively affected in FAW fed on potato and tobacco. Our results support the preference-performance hypothesis, that is, that herbivore females maximize fitness by choosing host plants associated with strong larval performance. Although larvae and adults performed poorly on potato and tobacco, their offspring will be capable of establishing populations on them, posing a potential threat to these crops in China.

The baroreflex afferent pathway plays a critical role in H2S-mediated autonomic control of blood pressure regulation under physiological and hypertensive conditions.

Hydrogen sulfide (H2S), which is closely related to various cardiovascular disorders, lowers blood pressure (BP), but whether this action is mediated via the modification of baroreflex afferent function has not been elucidated. Therefore, the current study aimed to investigate the role of the baroreflex afferent pathway in H2S-mediated autonomic control of BP regulation. The results showed that baroreflex sensitivity (BRS) was increased by acute intravenous NaHS (a H2S donor) administration to renovascular hypertensive (RVH) and control rats. Molecular expression data also showed that the expression levels of critical enzymes related to H2S were aberrantly downregulated in the nodose ganglion (NG) and nucleus tractus solitarius (NTS) in RVH rats. A clear reduction in BP by the microinjection of NaHS or L-cysteine into the NG was confirmed in both RVH and control rats, and a less dramatic effect was observed in model rats. Furthermore, the beneficial effects of NaHS administered by chronic intraperitoneal infusion on dysregulated systolic blood pressure (SBP), cardiac parameters, and BRS were verified in RVH rats. Moreover, the increase in BRS was attributed to activation and upregulation of the ATP-sensitive potassium (KATP) channels Kir6.2 and SUR1, which are functionally expressed in the NG and NTS. In summary, H2S plays a crucial role in the autonomic control of BP regulation by improving baroreflex afferent function due at least in part to increased KATP channel expression in the baroreflex afferent pathway under physiological and hypertensive conditions.

Relationship between Methylation of FHIT and CDH13 Gene Promoter Region and Liver Cancer.

In order to demonstrate the relationship between methylation of fragile histidine triad (FHIT) and T-cadherin/H-cadherin (CDH13) genes and liver cancer, the methylation status of FHIT and CDH13 was detected in healthy individuals and in Mongolian and Han patients with liver cancer. The phenol-chloroform method was used to extract genomic DNA. The methylation specific polymerase chain reaction method was applied to detect the methylation status of FHIT and CDH13. The relationship between smoking and alcohol consumption and gene (FHIT and CDH13) methylation was analyzed. There was significant difference in methylation rate of FHIT (72.67%, 34.67%) and CDH13 (72.0%, 28.0%) between liver cancer patients and healthy individuals of Mongolian descent (P<0.05), as well as that of FHIT (68%, 30.67%) and CDH13 (64%, 26%) between liver cancer patients and healthy individuals of Han individuals (P<0.05). There was also a relationship between smoking and drinking and the methylation of FHIT and CDH13 (P<0.05). Thus, the methylation of FHIT and CDH13 had a relationship with liver cancer incidence. Smoking and alcohol ingestion may promote the methylation of FHIT and CDH13.