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The Klotho loss-of-function mutation is known to cause accelerated senescence in many organs, but its effects on the cornea have not been published. The present study aims to investigate the effects of the Klotho null mutation on cornea degeneration and to characterize the pathological features. Mouse corneas of Klotho homozygous, heterozygous, and wild-type mice at 8 weeks of age for both genders were subject to pathological and immunohistological examinations. The results show an irregular topography on the corneal surface with a Klotho null mutation. Histological examinations revealed a reduced corneal epithelial cell density, endothelial cell-shedding, and decreased cornea stromal layer thickness in the absence of the Klotho function. Furthermore, guttae formation and the desquamation of wing cells were significantly increased, which was comparable to the characteristics of Fuchs endothelial corneal dystrophy and bullous keratopathy. The mechanism analysis showed multi-fold abnormalities, including oxidative stress-induced cornea epithelium apoptosis and inflammation, extracellular matrix remodeling in the stroma, and a disruption of epithelial repair, presumably through the epithelial-mesenchymal transition. In conclusion, cornea degeneration was observed in the Klotho loss-of-function mutant mice. These pathological features support the use of Klotho mutant mice for investigating age-related cornea anomalies, including Fuchs endothelial corneal dystrophy, bullous keratopathy, and dry eye diseases.

The Klotho null mutation is known to lead to accelerated aging in many organs, but its effects on tear secretion and lacrimal gland (LG) senescence have not been addressed. This study investigated whether the Klotho null mutation would lead to a dry eye status and the outcome of LG without Klotho function. The Klotho ( -/- ) mutant mice showed reduced LG size and tear volume on the 8th week, as compared to their littermates ( +/+, +/- ). Hematoxylin-Eosin and Masson's trichrome staining were performed to determine morphological changes and collagen deposition. Traits of LG aging, including acinar atrophy, thickened capsules, and more collagen depositions, were observed. Immunohistochemical detections for Klotho, α-SMA, MDA, 8-OHdG, vasoactive intestinal polypeptide (VIP), tyrosine hydroxylase (TH), MMP-2, MMP-9, and FGF-23 were performed and compared among the three genotypes ( +/+ , +/- , -/- ) at 6 and 8 weeks of age for mechanism analyses. Unexpectedly, the Klotho protein was not detected in the LG of all the three genotypes, indicating indirect effects from the Klotho null mutation. Further analyses showed abundant MDA and 8-OHdG detected in the Klotho ( -/- ) LG on the 8th week, indicating elevated oxidative stress. In addition, both sympathetic and parasympathetic neural transducing activities, as represented by TH and VIP expression, respectively, and α-SMA were increased in LGs with Klotho mutations. Furthermore, MMP-2 and MMP-9 expression were elevated, with FGF-23 expression being decreased on the 8th week in the Klotho ( -/- ) LG. In conclusion, characteristics of age-related LG degeneration were found in the Klotho null mutant mice. These traits support the use of Klotho mutant mice as a model of age-related dry eye disease.

Chronic inflammatory airway diseases, characterized by airway inflammation and airway remodelling, are increasing as a cause of morbidity and mortality for all age groups and races across the world. The underlying molecular mechanisms involved in chronic inflammatory airway diseases have not been fully explored. MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) have recently attracted much attention for their roles in the regulation of a variety of biological processes. A number of studies have confirmed that both lncRNAs and miRNAs can regulate the initiation and progression of chronic airway diseases by targeting mRNAs and regulating different cellular processes, such as proliferation, apoptosis, inflammation, migration, and epithelial-mesenchymal transition (EMT). Recently, accumulative evidence has shown that the novel regulatory mechanism underlying the interaction among lncRNAs, miRNAs and messenger RNAs (mRNAs) plays a critical role in the pathophysiological processes of chronic inflammatory airway diseases. In this review, we comprehensively summarized the regulatory roles of the lncRNA-miRNA-mRNA network in different cell types and their potential roles as biomarkers, indicators of comorbidities or therapeutic targets for chronic inflammatory airway diseases, particularly chronic obstructive pulmonary disease (COPD) and asthma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Qiao, Hou, He, Song, An, Altawil, Zhou, Wang, Kang and Yin.)

Introduction: Cholecystokinin type 2 receptor (CCK2R), which mediates the action of gastrin and cholecystokinin (CCK), has been demonstrated to promote the proliferation of colorectal cancer (CRC). A number of studies showed that CCK2R overexpressed in gastric cancer and pancreatic cancer but few in CRC. The correlation between CCK2R expression and clinicopathological characteristics is also not clear., Methods: This study investigated CCK2R expression in a wide range of cell lines and clinical CRC samples, and explored expression pattern and prognostic value of CCK2R in relation to clinicopathological parameters. The location and expression levels of CCK2R were measured by immunocytochemical (ICC), qRT-PCR and Western blot. The druggability and antineoplastic effects of CCK2R as a therapeutic target were investigated using an anti-CCK2R targeting recombinant toxin named rCCK8PE38 by CCK-8 assay., Results: Compared with paracarcinoma tissues, tumor samples showed overexpression of CCK2R (p = 0.028) including both CRC tissue and plasma samples, with plasma detection showing a significant indication for CCK2R evaluation. Aberrant expression correlated significantly with histological type (p = 0.032) and p53 status (p < 0.01), and patients with CCK2R overexpression had significantly lower disease-free survival. Application of rCCK8PE38 demonstrated the specificity and druggability of CCK2R as a therapeutic target, providing a strategy for clinical case screening of drugs targeting CCK2R., Conclusion: This study highlighted the aberrant expression and clinical correlation of CCK2R and reveals its diagnostic, prognostic and treatment value in CRC. We hypothesize that CCK2R serve as a target for the diagnosis and treatment of this cancer.

Background: Emerging evidence indicate that miRNAs play an important role on gastric cancer (GC) progression via regulating several downstream targets, but it is still partially uncovered. This study aimed to explore the molecular mechanisms of GC by comprehensive analysis of mRNAs and miRNA expression profiles., Methods: The mRNA and miRNA expression profiles of GSE79973 and GSE67354 downloaded from Gene Expression Omnibus were used to analyze the differentially expressed genes (DEGs) and DE-miRNAs among GC tissues and normal tissues. Then, targets genes of DE-miRNAs were predicted and the DE-miRNA-DEG regulatory network was constructed. Next, function enrichment analysis of the overlapped genes between the predicted DE-miRNAs targets and DEGs was performed and a protein-protein interactions network of overlapped genes was constructed. Finally, RT-PCR analysis was performed to detect the expression levels of several key DEGs and DE-miRNAs., Results: A set of 703 upregulated and 600 downregulated DEGs, as well as 8 upregulated DE-miRNAs and 27 downregulated DE-miRNAs were identified in GC tissue. hsa-miR-193b-3p and hsa-miR-148a-3p, which targeted most DEGs, were highlighted in the DE-miRNA-DEG regulatory network, as well as hsa-miR-1179, which targeted KNL1, was newly predicted to be associated with GC. In addition, NCAPG, which is targeted by miR-193b-3p, and KNL1, which is targeted by hsa-miR-1179, had higher degrees in the PPI network. RT-qPCR results showed that hsa-miR-148a-3p, hsa-miR-193b-3p, and hsa-miR-1179 were downregulated, and NCAPG and KNL1 were upregulated in GC tissues; this is consistent with our bioinformatics-predicted results., Conclusions: The downregulation of miR-193b-3p might contribute to GC cell proliferation by mediating the upregulation of NCAPG; as additionally, the downregulation of miR-193b-3p might contribute to the mitotic nuclear division of GC cells by mediating the upregulation of KNL1.

Objective: In previous studies, Lactobacillus plantarum ZJ316 showed probiotic properties, such as antimicrobial activity against various pathogens and the capacity to significantly improve pig growth and pork quality. The purpose of this study was to reveal the genes potentially related to its genetic adaptation and probiotic profiles based on comparative genomic analysis., Methods: The genome sequence of L. plantarum ZJ316 was compared with those of eight L. plantarum strains deposited in GenBank. BLASTN, Mauve, and MUMmer programs were used for genome alignment and comparison. CRISPRFinder was applied for searching the clustered regularly interspaced short palindromic repeats (CRISPRs)., Results: We identified genes that encode proteins related to genetic adaptation and probiotic profiles, including carbohydrate transport and metabolism, proteolytic enzyme systems and amino acid biosynthesis, CRISPR adaptive immunity, stress responses, bile salt resistance, ability to adhere to the host intestinal wall, exopolysaccharide (EPS) biosynthesis, and bacteriocin biosynthesis., Conclusions: Comparative characterization of the L. plantarum ZJ316 genome provided the genetic basis for further elucidating the functional mechanisms of its probiotic properties. ZJ316 could be considered a potential probiotic candidate.

The aim of this study is to investigate the antimicrobial potential of Lactobacillus plantarum ZJ5, a strain isolated from fermented mustard with a broad range of inhibitory activity against both Gram-positive and Gram-negative bacteria. Here we present the peptide plantaricin ZJ5 (PZJ5), which is an extreme pH and heat-stable. However, it can be digested by pepsin and proteinase K. This peptide has strong activity against Staphylococcus aureus. PZJ5 has been purified using a multi-step process, including ammonium sulfate precipitation, cation-exchange chromatography, hydrophobic interactions and reverse-phase chromatography. The molecular mass of the peptide was found to be 2572.9 Da using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The primary structure of this peptide was determined using amino acid sequencing and DNA sequencing, and these analyses revealed that the DNA sequence translated as a 44-residue precursor containing a 22-amino-acid N-terminal extension that was of the double-glycine type. The bacteriocin sequence exhibited no homology with known bacteriocins when compared with those available in the database, indicating that it was a new class IId bacteriocin. PZJ5 from a food-borne strain may be useful as a promising probiotic candidate.

In a further study of the thermal development of fingermarks on paper and similar surfaces, it is demonstrated that direct contact heating of the substrate using coated or ceramic surfaces at temperatures in excess of 230°C produces results superior to those obtained using hot air. Fingermarks can also be developed in this way on other cellulose-based substrates such as wood and cotton fabric, though ridge detail is difficult to obtain in the latter case. Fluorescence spectroscopy indicates that the phenomena observed during the thermal development of fingermarks can be reproduced simply by heating untreated white copy paper or filter paper, or these papers treated with solutions of sodium chloride or alanine. There is no evidence to suggest that the observed fluorescence of fingermarks heated on paper is due to a reaction of fingermark constituents on or with the paper. Instead, we maintain that the ridge contrast observed first as fluorescence, and later as brown charring, is simply an acceleration of the thermal degradation of the paper. Thermal degradation of cellulose, a major constituent of paper and wood, is known to give rise to a fluorescent product if sufficient oxygen is available [1-5]. However, the absence of atmospheric oxygen has only a slight effect on the thermal development of fingermarks, indicating that there is sufficient oxygen already present in paper to allow the formation of the fluorescent and charred products. In a depletion study comparing thermal development of fingermarks on paper with development using ninhydrin, the thermal technique was found to be as sensitive as ninhydrin for six out of seven donors. When thermal development was used in sequence with ninhydrin and DFO, it was found that only fingermarks that had been developed to the fluorescent stage (a few seconds of heating) could subsequently be developed with the other reagents. In the reverse sequence, no useful further development was noted for fingermarks that were treated thermally after having been developed with ninhydrin or DFO. Aged fingermarks, including marks from 1-year-old university examination papers were successfully developed using the thermal technique., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Aim: To study the blocking effects of genistein on cell proliferation cycle in human gastric carcinoma cells (SGC-7901) and the possible mechanism., Methods: MTT assay was applied in the detection of the inhibitory effects of genistein on cell proliferation. Flow cytometry was used to analyze the cell cycle distribution. Immunocytochemical technique and Western blotting were performed to detect the protein expression of cyclin D1, cyclin B1 and p21(waf1/cip1)., Results: Genistein significantly inhibited the growth and proliferation of human gastric carcinoma cells (SGC-7901). Seven days after treatment with different concentrations of genistein (2.5, 5.0, 10.0, 20.0 microg/mL), the growth inhibitory rates were 11.2%, 28.8%, 55.3%, 84.7% respectively and cell cycles were arrested at the G(2)/ M phase. Genistein decreased cyclin D1 protein expression and enhanced cyclin B1 and p21(waf/cip1) protein expression in a concentration-dependent manner., Conclusion: The growth and proliferation of SGC-7901 cells can be inhibited by genistein via blocking the cell cycle, with reduced expression of cyclin D1 and enhanced expression of cyclin B1 and p21(waf/cip1) protein in the concentration range of 0-20 microg/mL.