Colorectal cancer (CRC) is one of the most common digestive malignant tumors, and DMTN is a transcriptionally differentially expressed gene that was identified using CRC mRNA sequencing data from The Cancer Genome Atlas (TCGA). Our preliminary work suggested that the expression of DMTN was downregulated in CRC, and the Rac1 signaling pathway was significantly enriched in CRC tissues with low DMTN expression. However, the specific functions and underlying molecular mechanisms of DMTN in the progression of CRC and the upstream factors regulating the downregulation of the gene remain unclear.

Hyperuricemia is an important potential pathogenic factor for hypertension, cardiovascular disease and stroke. The current study aimed to investigate the prevalence of hyperuricemia and its relationship to lifestyle characteristics and dietary habits in centenarians and near-centenarians.

Perineural invasion (PNI), as a key pathological feature of tumor spread, has emerged as an independent prognostic factor in patients with rectal cancer (RC). The preoperative stratification of RC patients according to PNI status is beneficial for individualized treatment and improved prognosis. However, the preoperative evaluation of PNI status is still challenging.

Ubinuclein-2 (UBN2) is a nuclear protein that interacts with many transcription factors. The molecular role and mechanism of UBN2 in the development and progression of cancers, including colorectal cancer (CRC), is not well understood. The current study explored the role of UBN2 in the development and progression CRC.

Epithelial dysfunction is a key characteristic of acute lung injury (ALI). Isoflurane (ISO) confers lung protection via anti-inflammatory and anti-apoptotic properties. However, the specific role and potential mechanisms of subanesthetic ISO in lung epithelium protection during zymosan-induced ALI remain unclear. In this study, zymosan increased the expression and activity of beneficial heme oxygenase-1 (HO-1) and signal transducers and activators of transcription 3 (STAT3) in the lung and isolated type II alveolar epithelial cells (AECs-II) from wild-type (WT) mice, which was further enhanced by ISO treatment. ISO reduced the mortality, lung edema, histological changes and pulmonary cell apoptosis, and simultaneously decreased total cells, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels in bronchoalveolar lavage fluid in the zymosan-stimulated WT mice but not in HO-1-deficient mice. Moreover, ISO abated zymosan-augmented lactate dehydrogenase activity, TNF-α and IL-1β production, and apoptosis in WT AECs-II but not in HO-1- or STAT3-silenced cells. Mechanisticly, the epithelial protective effects of ISO on zymosan insult in vivo and in vitro were mediated by a positive feedback loop comprising STAT3 and HO-1. Pro-survival and anti-apoptosis by ISO was highly reliant on activated STAT3, involving in downstream Akt activation and reduced ratio of pro-apoptotic/anti-apoptotic molecules. Overall, HO-1/STAT3 signaling is in favor of lung epithelial protection of ISO in zymosan-challenged mice, suggesting ISO as a valuable therapeutic agent for ALI.

The onset of distal metastasis, which underlies the high mortality of breast cancers, warrants substantial studies to depict its molecular basis. Nuclear factor of activated T cells 5 (NFAT5) is upregulated in various malignancies and is critically involved in migration and invasion of neoplastic cells. Nevertheless, the metastasis-related events potentiated by this transcriptional factor and the mechanism responsible for NFAT5 elevation in carcinoma cells remain to be fully elucidated.

Transducin-like enhancer of Split3 (TLE3) serves as a transcriptional corepressor during cell differentiation and shows multiple roles in different kinds of cancers. Recently, TLE3 together with many other genes involved in Wnt/β-catenin pathway were detected hyper-methylated in colorectal cancer (CRC). However, the potential role and the underlying mechanism of TLE3 in CRC progression remain scarce.

Ubiquitin-specific protease 22 (USP22) aberrance has been implicated in several malignancies; however, whether USP22 plays a role in anaplastic thyroid carcinoma (ATC) remains unclear. Here, we report that USP22 expression is highly elevated in ATC tissues, which positively correlated with tumor size, extracapsular invasion, clinical stages, and poor prognosis of ATC patients. In vitro assays showed that USP22 depletion suppressed ATC cell survival and proliferation by decreasing Rb phosphorylation and cyclin D2, inactivating Akt, and simultaneously upregulating Rb; USP22 silencing restrained cell migration and invasion by inhibiting epithelial-mesenchymal transition; USP22 knockdown promoted mitochondrion- mediated and caspase-dependent apoptosis by upregulating Bax and Bid and promoting caspase-3 activation. Consistent with in vitro findings, downregulation of USP22 in ATC cells impeded tumor growth and lung metastasis in vivo. These results raise the applicability for USP22 as a useful predictor of ATC prognosis and a potential therapeutic target for ATC.

There are more than 300 genetic loci that have been found to be related to hereditary hearing impairment (HHI), including 92 causative genes for nonsyndromic hearing loss, among which 34 genes are related to autosomal dominant nonsyndromic HHI (ADNSHHI). Traditional linkage analysis and candidate gene sequencing are not effective at detecting the ADNSHHI, especially for the unconditional families that may have more than one pathogenic cause. This study identified two disease-causing genes TJP2 and GJB2 in a Chinese family with unconditional ADNSHHI.

A pair of cobalt(II)-based hydrogen-bonded organic frameworks (HOFs), [Co(pca)2(bmimb)]n (1) and [Co2(pca)4(bimb)2] (2), where Hpca = p-chlorobenzoic acid, bmimb = 1,3-bis((2-methylimidazol-1-yl)methyl)benzene, and bimb = 1,4-bis(imidazol-1-ylmethyl)benzene were hydrothermally synthesized and characterized through infrared spectroscopy (IR), elemental and thermal analysis (EA), power X-ray diffraction (PXRD), and single-crystal X-ray diffraction (SCXRD) analyses. X-ray diffraction structural analysis revealed that 1 has a one-dimensional (1D) infinite chain network through the deprotonated pca- monodentate chelation and with a μ2-bmimb bridge Co(II) atom, and 2 is a binuclear Co(II) complex construction with a pair of symmetry-related pca- and bimb ligands. For both 1 and 2, each cobalt atom has four coordinated twisted tetrahedral configurations with a N2O2 donor set. Then, 1 and 2 are further extended into three-dimensional (3D) or two-dimensional (2D) hydrogen-bonded organic frameworks through C-H···Cl interactions. Topologically, HOFs 1 and 2 can be simplified as a 4-connected qtz topology with a Schläfli symbol {64·82} and a 4-connected sql topology with a Schläfli symbol {44·62}, respectively. The fluorescent sensing application of 1 was investigated; 1 exhibits high sensitivity recognition for Fe3+ (Ksv: 10970 M-1 and detection limit: 19 μM) and Cr2O72- (Ksv: 12960 M-1 and detection limit: 20 μM). This work provides a feasible detection platform of HOFs for highly sensitive discrimination of Fe3+ and Cr2O72- in aqueous media.

Accurate estimation of the glomerular filtration rate (GFR) and staging of chronic kidney disease (CKD) are important. Currently, there is no research on the differences in several estimated GFR equations for staging CKD in a large sample of centenarians. Thus, this study aimed to investigate the differences in CKD staging with the most commonly used equations and to analyze sources of discrepancy.

Mutations in OTOF gene, encoding otoferlin, cause DFNB9 deafness and non-syndromic auditory neuropathy (AN). The aim of this study is to identify OTOF mutations in Chinese patients with non-syndromic auditory neuropathy.

Neutrophil release of NO/ONOO- induces endothelial cell barrier dysfunction in inflammatory acute lung injury (ALI). Previous studies using zymosan-triggered inflammation and ALI model revealed that zymosan promotes inducible NO synthase (iNOS) expression in neutrophils, and that isoflurane inhibits zymosan-induced oxidative stress and iNOS biosynthesis. However, the underlying mechanisms remain largely unknown. We found here that in zymosan-primed neutrophils, iNOS is transcriptionally activated by NF-κB, whose nuclear translocation is triggered by excessive reactive oxygen species (ROS) and consequently activated p38 MAPK. ROS production is attributed to zymosan-initiated Toll-like receptor 2 (TLR2) signaling, in which the adaptor MyD88 recruits and activates c-Src, and c-Src activates NADPH oxidase to generate ROS. Subanesthetic isoflurane counteracts the aforementioned zymosan-induced signaling by targeting N-methyl-D-aspartic acid (NMDA) glutamate receptor and thereby suppressing calcium influx and c-Src activation. Whereas iNOS accelerates NO/ONOO- production in neutrophils which eventually promote protein leak from pulmonary microvascular endothelial cells (PMVEC), isoflurane reduced NO/ONOO- release from zymosan-treated neutrophils, and thus relieves trans-PMVEC protein leak. This study provides novel insights into the roles of neutrophils and the underlying mechanisms in zymosan-induced ALI, and has implications for the therapeutic potential of subanesthetic isoflurane in attenuating inflammatory responses causing lung endothelial cell damage.

Previous studies reported that low level of oestradiol (E2) was associated with higher risk of cardiovascular disease (CVD). However, little study examined the relationship between E2 and CVD in longevous women, which were deficient in serum E2 for the post-menopausal status. Therefore, this study aims to explore the association between E2 and CVD risk factors in a group of female centenarians of Hainan, China.

Increasing evidence suggests that regular physical exercise suppresses chronic inflammation. However, the potential inhibitory effects of swimming on dextran sulfate sodium (DSS)-induced chronic colitis, and its underlying mechanisms, remain unclear. In this study, rats were orally administered DSS to induce chronic colitis, and subsequently treated with or without swimming exercise. A 7-week swimming program (1 or 1.5 hours per day, 5 days per week) ameliorated DSS-caused colon shortening, colon barrier disruption, spleen enlargement, serum LDH release, and reduction of body weight gain. Swimming for 1.5 hours per day afforded greater protection than 1 hour per day. Swimming ameliorated DSS-induced decrease in crypt depth, and increases in myeloperoxidase activity, infiltration of Ly6G+ neutrophils and TNF-α- and IFN-γ-expressing CD3+ T cells, as well as fecal calprotectin and lactoferrin. Swimming inhibited pro-inflammatory cytokine and chemokine production and decreased the protein expression of phosphorylated nuclear factor-κB p65 and cyclooxygenase 2, whereas it elevated interleukin-10 levels. Swimming impeded the generation of reactive oxygen species, malondialdehyde, and nitric oxide; however, it boosted glutathione levels, total antioxidant capacity, and superoxide dismutase and glutathione peroxidase activities. Additionally, swimming decreased caspase-3 activity and expression of apoptosis-inducing factor, cytochrome c, Bax, and cleaved-caspase-3, but increased Bcl-2 levels. Overall, these results suggest that swimming exerts beneficial effects on DSS-induced chronic colitis by modulating inflammation, oxidative stress, and apoptosis.