Genome-wide analysis of two different regions of brain reveals the molecular changes of fertility related genes in rln3a-/- mutants in male Nile tilapia (Oreochromis niloticus).

Relaxin3 (rln3) has been associated with various emotional and cognitive processes, including stress, anxiety, learning, memory, motivational behavior, and circadian rhythm. Notably, previous report revealed that Rln3a played an indispensable role in testicular development and male fertility in Nile tilapia (Oreochromis niloticus). However, the underlying molecular mechanisms remain largely unknown. We found that Rln3a is expressed exclusively in the diencephalon* (Di*) of the brain. Deficiency of Rln3a resulted in a significant increase in serum dopamine level and an upregulation of gene expression of gnrh1 and kisspeptin2. To further elucidate the role of Rln3a in fish fertility, we collected two different regions of Di* and hypothalamus (Hyp) tissues for subsequent RNA-seq analysis of both wild-type (rln3a+/+) and rln3a-/- male tilapia. Upon the transcriptomic data, 1136 and 755 differentially expressed genes (DEGs) were identified in the Di* and Hyp tissues, respectively. In Di*, the up-regulated genes were enriched in circadian rhythm, chemical carcinogenesis, while the down-regulated genes were enriched in type II diabetes mellitus, dopaminergic synapse, and other pathways. In Hyp, the up-regulated genes were enriched in circadian rhythm, pyrimidine metabolism, while the down-regulated genes were enriched in type I diabetes mellitus, autoimmune thyroid disease, and other pathways. Subsequently, the results of both qRT-PCR and FISH assays highlighted a pronounced up-regulation of core circadian rhythm genes, cry1b and per3, whereas genes such as clocka, clockb, and arntl exhibited down-regulation. Furthermore, the genes associated with dopamine biosynthesis were significantly increased in the Hyp. In summary, the mutation of rln3a in male tilapia resulted in notable changes in circadian rhythm and disease-linked signaling pathways in the Di* and Hyp. These changes might account for the fertility defects observed in rln3a-/- male mutants in tilapia.

A New Method for Constructing Macrophage-Associated Predictors of Treatment Efficacy Based on Single-Cell Sequencing Analysis.

Tumor-associated macrophages (TAMs) are highly infiltrated in the tumor microenvironment (TME) of colorectal cancer (CRC) and play a vital role in CRC's development as well as prognosis. The required data were obtained from the Gene Expression Omnibus database and The Cancer Genome Atlas. Univariate Cox regression and least absolute shrinkage operator analyses were executed for model construction. TME assessment and immune prediction were performed using the ESTIMATE software package and the single sample genome enrichment analysis algorithm. The results show patients with low a TAMs risk score (TRS) had a better prognosis in both The Cancer Genome Atlas and Gene Expression Omnibus cohorts. Patients with low TRS were more sensitive to 3 chemotherapeutic agents: oxaliplatin, paclitaxel, and cisplatin ( P <0.05). TME assessment showed that the low TRS group had less infiltration of M2 macrophages and regulatory T cells, but CD4 + T cells, NK cells, and dendritic cells occupy a greater proportion of TME. Low TRS group patients have a low StromalScore and ImmuneScore but have high TumorPurity. The immune checkpoint TIM-3 gene HAVCR2 expression was significantly higher in the high TRS group. Finally, we created a nomogram including TRS for forecasting survival, and TRS was significantly associated with the clinical stage of the patients. In conclusion, the TRS serves as a reliable prognostic indicator of CRC; it predicts patient outcomes to immunotherapy and chemotherapy and provides genomic evidence for the subsequent development of modulated TAMs for treating CRC.

Schisandrin B inhibits tumor progression of hepatocellular carcinoma by targeting the RhoA/ROCK1 pathway.

Background: Schisandrin B (Sch. B) performs various pharmacological properties, including anticancer activities. However, the pharmacological mechanisms of Sch. B in hepatocellular carcinoma (HCC) are not fully elucidated. We investigated the impact and mechanism on progression in HCC, and to provide new experimental evidence for HCC treatment. Methods: To determine the inhibitory effect of Sch. B on HCC in vivo, 32 Balb/c nude mice were used to prepare the tumor-bearing mice model by subcutaneously inoculating HCC cells (Huh-7). As tumor volume grew to 100 mm3, mice were randomly divided into Saline (control group), 100 mg/kg Sch. B group (Sch. B-L), 200 mg/kg Sch. B group (Sch. B-M), and 400 mg/kg Sch. B group (Sch. B-H) (n=8). Saline or different concentration Sch. B was used to treat mice via gavage administration for 21 days. After mice were euthanized, tumor weight and volume were evaluated. Cell apoptosis was detected by TUNEL. Ki-67 and PCNA were detected by immunohistochemical staining. The RhoA and Rho-associated protein kinase 1 (ROCK1) were determined by western blot. In vitro experiment, Huh-7 cell were treated by Sch. B at 40, 30, 20, 10, 5, 1, and 0 µM to detect cell proliferation by Cell Counting Kit-8 (CCK-8). Huh-7 cells were divided as a control group, Sch. B group, and Sch. B + RhoA overexpression (Sch. B + RhoA) group. RhoA and ROCK1 were examined. The colony formation assay and flow cytometry were used to detect cell proliferation and apoptosis. The wound healing and Transwell assays were used for cell metastasis detection. Results: Our results showed 100, 200 and 400 mg/kg Sch. B significantly reduced tumor weight and volume. And 200 and 400 mg/kg Sch. B increased apoptosis, and reduced Ki-67 and PCNA levels, inhibited the RhoA and ROCK1 in vivo (P<0.05). In vitro experiment, Sch. B inhibited Huh-7 cell proliferation at concentration more than 10 µM (P<0.05). Sch. B decreased cell duplication, promoted apoptosis and blocked migration and invasion of Huh-7 (P<0.05). Sch. B inhibited RhoA and ROCK1 level as compared with control group (P<0.05). RhoA overexpression reversed the effect of Sch. B (P<0.05). Conclusions: Sch. B inhibits Huh-7 cells progression via RhoA/ROCK1 pathway. The results provide new evidence for the clinical treatment of HCC.

Hair follicle mesenchymal stem cell exosomal lncRNA H19 inhibited NLRP3 pyroptosis to promote diabetic mouse skin wound healing.

Skin wounds caused by diabetes are a major medical problem. Mesenchymal stem cell-derived exosomes hold promise to quicken wound healing due to their ability to transfer certain molecules to target cells, including mRNAs, microRNAs, lncRNAs, and proteins. Nonetheless, the specific mechanisms underlying this impact are not elucidated. Therefore, this research aimed to investigate the effect of MSC-derived exosomes comprising long non-coding RNA (lncRNA) H19 on diabetic skin wound healing. Hair follicle mesenchymal stem cells (HF-MSCs) were effectively isolated and detected, and exosomes (Exo) were also isolated smoothly. Pretreatment with 30 mM glucose for 24 h (HG) could efficiently induce pyroptosis in HaCaT cells. Exosomal H19 enhanced HaCaT proliferation and migration and inhibited pyroptosis by reversing the stimulation of the NLRP3 inflammasome. Injection of exosomes overexpressing lncRNA H19 to diabetic skin wound promoted sustained skin wound healing, whereas sh-H19 exosomes did not have this effect. In conclusion, Exosomes overexpressing H19 promoted HaCaT proliferation, migration and suppressed pyroptosis both in vitro and in vivo. Therefore, HFMSC-derived exosomes that overexpress H19 may be included in strategies for healing diabetic skin wounds.

Single-nucleotide polymorphisms of TLR4 and GAS7 linked to primary open-angle glaucoma among patients of Shenyang, China.

The potential for adverse outcomes and classifications of glaucoma differ among race, country, gender, and family medical history. Nearly, 50 represent candidate genes are considered as potential contributors to the happening for the primary open-angle glaucoma (POAG) since the advent of GWASs. Our investigation is the first to report the Toll-like receptor 4 (TLR4) and growth arrest-specific 7 (GAS7) among people in Shenyang, China; to investigate whether single-nucleotide polymorphisms (SNPs) in (TLR4) or GAS7 gene are risk factors for POAG among people in Shenyang, China; and also to explore their potential pathogenic mechanisms. POAG patients from July 2015 to June 2019 at Shenyang Fourth People's Hospital were selected. A total of 218 POAG patients and 252 controls were enrolled. Eight potentially functional SNPs of TLR4 (rs7868859, rs7873784, rs77358523, and rs752998) and GAS7 (rs8012311, rs11656696, rs74629981, and rs9900085) were genotyped. Multifactor analysis was conducted to evaluate the correlation between TLR4, GAS7, and POAG. The allele frequency of rs7873784 of TLR4 demonstrated that the GC (P = 0.030), CC (P = 0.040), and GC + CC genotypes (P = 0.009) were significantly higher compared with CC genotype for POAG patients than that for controls. The rs8072311 and rs9900085 of GAS7 gene also were significantly associated with POAG. Haplotype analysis found that the C-A-T-A haplotype (order: rs7873784-rs77358523-rs752998-rs7868859) of TLR4 gene and the two haplotypes A-C-C-A and C-C-A-C of GAS7 (order: rs9900085-rs74629981-rs8072311-rs11656696) were associated with an elevated susceptibility to POAG (P < 0.05). In this study, rs7868859 of TLR4 and rs8012311 and rs9900085 polymorphisms of GAS7 were first identified to be related to POAG among people in Shenyang, China.

Enhanced visible light activated hydrogen evolution activity over cadmium sulfide nanorods by the synergetic effect of a thin carbon layer and noble metal-free nickel phosphide cocatalyst.

Photocatalytic water splitting is considered to be a promising strategy for addressing the global energy crisis through the expanded use of solar energy. Herein, cadmium sulfide (CdS) nanorods modified with a thin conductive carbon layer and a nickel phosphide co-catalyst, referred to as cadmium sulfide coated with a carbon layer and nickel phosphide (CdS@C/Ni2P, where @ indicates a core-shell structure), were synthesized and applied as a novel composite photocatalyst for water splitting. The optimized CdS@C/Ni2P composite showed a high photocatalytic hydrogen generation rate of 32030 µmol h-1 g-1, which was approximately 19 times as high as that of pure CdS. We believed that the thin carbon layer acted as an electron acceptor to promote charge transfer and protect the CdS nanorods from photocorrosion. In addition, the surface loading of the nickel phosphide (Ni2P) cocatalyst was able to further draw photogenerated electrons from the cadmium sulfide coated with a carbon layer (CdS@C) heterojunction and provide active sites for hydrogen evolution. Thus, greatly enhanced hydrogen generation was achieved through a combination of carbon coating and surface cocatalyst loading. This development provides a new way to design composite photocatalysts with multiple junctions for efficient water splitting performance.

Noble-metal-free nickel phosphide modified CdS/C3N4 nanorods for dramatically enhanced photocatalytic hydrogen evolution under visible light irradiation.

Photocatalytic hydrogen evolution is a promising technology in solving the global energy and environment issues. Therefore, it is urgent to develop highly efficient, nonprecious metal and stable photocatalysts. In this work, we synthesized a highly efficient Ni2P-CdS/g-C3N4 composite based on the concept of combining heterojunction engineering with co-catalyst modification. When employed as a photocatalyst for water splitting, the obtained best composite (5% Ni2P-CdS/g-C3N4) displayed dramatically enhanced hydrogen evolution activity at the rate of 44 450 µmol h-1 g-1, which was about 27 times higher than that of pure CdS (1668 µmol h-1 g-1). The apparent quantum yield at 420 nm reaches 46.3%. The excellent photocatalytic activity and stability can be ascribed to the synergistic effect of the intimate contact between CdS and g-C3N4 and the surface co-catalyst modification. Specifically, the g-C3N4 coated on the CdS nanorods can effectively promote the electron-hole pair separation spatially and Ni2P can lower the overpotential of H+ reduction.

Comparison of central corneal thickness using ultrasound pachymetry during corneal collagen cross-linking.

PURPOSE: To study variation in central corneal thickness (CCT) during corneal collagen cross-linking(CXL) using ultrasound pachymetry. METHODS: Twenty patients (26 eyes) with progressing keratoconus undergoing riboflavin-UVA-induced CXL were involved in this study. Intraoperative CCT measurement using ultrasonic pachymetry was performed during the procedure. Measurements were obtained before operation, after epithelial removal, after riboflavin drop instillation, and after UVA irradiation. RESULTS: Mean CCT was 495 +/- 56 and 450 +/- 52 microm before and after epithelial removal, respectively. Mean CCT was 443 +/- 42 and 411 +/- 39 microm after riboflavin drop instillation and after UVA irradiation, respectively. Statistically significant decreases in CCT occurred between the preoperative period and after epithelial removal, after riboflavin drop instillation and after UVA irradiation. Twenty-six eyes from 20 patients undergoing CXL were divided into 2 groups (I with CCT > or = 400 microm after UVA irradiation and II with CCT < 400 microm after UVA irradiation). No statistically significant difference was noted between I and II in preoperative endothelial cell count, but a statistically greater postoperative endothelial cell count was noted in I compared to II. A statistically significant difference was evident between preoperative and postoperative endothelial cell counts in Group II (P < 0.05). CONCLUSION: Performing CXL with the use of riboflavin and UVA irradiation resulted in a statistically significant decrease in CCT, to a level where the corneal endothelium may be damaged.