Breast cancer is a kind of common female cancers. Increasing evidence has exhibited that lncRNAs exert a crucial role in breast cancer. So far, the mechanism of lncRNAs in breast cancer is still not ...well established. In our current study, we focused on the biological role of lncRNA Nuclear Enriched Abundant Transcript 1 (NEAT1) in breast cancer. We observed that NEAT1 levels were significantly increased in human breast cancer cells including MCF‐7, MDA‐MB‐453, MDA‐MB‐231, and SKBR3 cells compared to normal mammary epithelial cells MCF‐10A while miR‐448 was decreased. We found that downregulation of NEAT1 was able to inhibit the growth of breast cancer cells and miR‐448 mimic exerted the similar function. Bioinformatics analysis and dual luciferase reporter assays confirmed the negative correlation between NEAT1 and miR‐448 in vitro. In addition, ZEB1 was predicted as a novel mRNA target of miR‐448. Overexpression of NEAT1 can induce breast cancer cell growth, migration, and invasion by inhibiting miR‐448 and upregulating ZEB1. It was demonstrated that NEAT1 can increase ZEB1 levels while miR‐448 mimic can repress ZEB1. It was speculated in our study that NEAT1 can serve as a competing endogenous lncRNA (ceRNA) to modulate ZEB1 by sponging miR‐448 in breast cancer. To conclude, we uncovered that NEAT1 participated in breast cancer progression by regulating miR‐448 and ZEB1. NEAT1 can be provided as a vital biomarker in breast cancer diagnosis and treatment therapy.
Our results implied that NEAT1 can play a significant role in breast cancer progression. We observed that NEAT1 downregulation could inhibit breast cancer progression. In addition, a reverse correlation between NEAT1 and miR‐448 was validated in our research, and ZEB1was concentrated on in our investigation asit can be targeted by miR‐448.
In this note, we study the stabilization problem of positive switched linear system (PSLS) with disturbance. By introducing a class of weak common linear copositive Lyapunov functions, we design ...time-dependent switching rules under which the system is asymptotically stable. Both continuous-time and discrete-time PSLS are taken into consideration, and the obtained results are also extended to nonpositive switched systems. Finally, the theoretical results are applied to consensus problem of multiagent systems with switching topologies and disturbance.
To investigate the effect of molecular hydrogen (H2) in a rat model subjected to optic nerve crush (ONC).
We tested the hypothesis that after optic nerve crush (ONC), retinal ganglion cell (RGC) ...could be protected by H₂. Rats in different groups received saline or hydrogen-rich saline every day for 14 days after ONC. Retinas from animals in each group underwent measurements of hematoxylin and eosin (H&E) staining, cholera toxin beta (CTB) tracing, gamma synuclein staining, and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) staining 2 weeks post operation. Flash visual evoked potentials (FVEP) and pupillary light reflex (PLR) were then tested to evaluate the function of optic nerve. The malondialdehyde (MDA) level in retina was evaluated.
H&E, gamma synuclein staining and CTB tracing showed that the survival rate of RGCs in hydrogen saline-treated group was significantly higher than that in saline-treated group. Apoptosis of RGCs assessed by TUNEL staining were less observed in hydrogen saline-treated group. The MDA level in retina of H₂ group was much lower than that in placebo group. Furthermore, animals treated with hydrogen saline showed better function of optic nerve in assessments of FVEP and PLR.
These results demonstrated that H₂ protects RGCs and helps preserve the visual function after ONC and had a neuroprotective effect in a rat model subjected to ONC.
To help doctors and patients evaluate lumbar intervertebral disc degeneration (IVDD) accurately and efficiently, we propose a segmentation network and a quantitation method for IVDD from T2MRI. A ...semantic segmentation network (BianqueNet) composed of three innovative modules achieves high-precision segmentation of IVDD-related regions. A quantitative method is used to calculate the signal intensity and geometric features of IVDD. Manual measurements have excellent agreement with automatic calculations, but the latter have better repeatability and efficiency. We investigate the relationship between IVDD parameters and demographic information (age, gender, position and IVDD grade) in a large population. Considering these parameters present strong correlation with IVDD grade, we establish a quantitative criterion for IVDD. This fully automated quantitation system for IVDD may provide more precise information for clinical practice, clinical trials, and mechanism investigation. It also would increase the number of patients that can be monitored.
Background
The missing asymptomatic COVID‐19 infections have been overlooked because of the imperfect sensitivity of the nucleic acid testing (NAT). Globally understanding the humoral immunity in ...asymptomatic carriers will provide scientific knowledge for developing serological tests, improving early identification, and implementing more rational control strategies against the pandemic.
Measure
Utilizing both NAT and commercial kits for serum IgM and IgG antibodies, we extensively screened 11 766 epidemiologically suspected individuals on enrollment and 63 asymptomatic individuals were detected and recruited. Sixty‐three healthy individuals and 51 mild patients without any preexisting conditions were set as controls. Serum IgM and IgG profiles were further probed using a SARS‐CoV‐2 proteome microarray, and neutralizing antibody was detected by a pseudotyped virus neutralization assay system. The dynamics of antibodies were analyzed with exposure time or symptoms onset.
Results
A combination test of NAT and serological testing for IgM antibody discovered 55.5% of the total of 63 asymptomatic infections, which significantly raises the detection sensitivity when compared with the NAT alone (19%). Serum proteome microarray analysis demonstrated that asymptomatics mainly produced IgM and IgG antibodies against S1 and N proteins out of 20 proteins of SARS‐CoV‐2. Different from strong and persistent N‐specific antibodies, S1‐specific IgM responses, which evolved in asymptomatic individuals as early as the seventh day after exposure, peaked on days from 17 days to 25 days, and then disappeared in two months, might be used as an early diagnostic biomarker. 11.8% (6/51) mild patients and 38.1% (24/63) asymptomatic individuals did not produce neutralizing antibody. In particular, neutralizing antibody in asymptomatics gradually vanished in two months.
Conclusion
Our findings might have important implications for the definition of asymptomatic COVID‐19 infections, diagnosis, serological survey, public health, and immunization strategies.
The combination of NAT and serological testing for IgM antibody significantly improves the detection sensitivity of asymptomatic COVID‐19 infections, compared with NAT alone. S1‐specific IgM antibody response with rapid emergence and disappearance might be helpful to assist NAT for early identification of infectious individuals. A majority of asymptomatics induce very low levels of neutralizing antibody that disappear in two months. Abbreviations: NAT, nucleic acid testing; FI, fluorescence intensity; NT50, half‐maximal neutralizing titer.
Migratory birds play an important role in the spread of multidrug-resistant (MDR) bacteria. To investigate the prevalence of MDR Escherichia coli in migratory birds in China and potential ...relationships with the environment, a total of 1387 samples (fecal samples, cloacal swabs, or throat swabs) were collected from migratory birds from three different river basins in China. The collected samples were processed and subjected to bacteriological examinations. Antimicrobial susceptibility testing of the recovered isolates was performed using the E-test for the detection of minimum inhibitory concentrations (MICs). Some antibiotic resistance genes were detected and the PCR products were confirmed by sequencing. In total, 478 (34.7%) E. coli isolates were recovered. The results showed that the drug-resistant E. coli isolates were highly resistant to β-lactams (43.7%) and tetracycline (22.6%), and 73 (15.3%) were MDR, including eight that were extended spectrum β-lactamase-positive. The retrieved strains harbored the blaCTX-M, blaTEM-1, tet(A), tet(B), tet(M), sul1, sul2, sul3, cmlA, floR, and intI1 genes with a prevalence of 5.9%, 36.4%, 80.5%, 11.9%, 6.8%, 6.8%, 47.5%, 12.7%, 50.8%, 37.3%, and 61.0%, respectively. The drug resistance rate of the isolates from southern China was higher than those from northern China. The E. coli samples collected for migratory birds in the Pearl River Basin had the highest proportion (46.7%) MDR isolates. Furthermore, MDR bacteria carried by migratory birds were closely related to the antibiotic content in the basin, which confirms that MDR bacteria carried by migratory birds are likely acquired from the environment. This study also confirmed that migratory birds are potential transmitters of MDR bacteria, demonstrating the need to reduce the use and emission of antibiotics and further in-depth studies on the mechanisms underlying drug resistance of bacteria.
Phylogeography has been one major focus of evolutionary biology in recent years, with many important advances in Chinese species. In this issue, we collected 11 phylogeographic studies of plants by ...Chinese laboratories. We further synthesized the main findings and patterns emerging from these and previous phylogeographic studies in China and asked where phylogeographic research should be directed in the coming years. Numerous examples have shown that phylogeographic patterns in China did not show an expected expansion–contraction pattern at large scale, mirroring the geological records showing that no unified ice sheet had developed in China during the Quaternary Period. Instead, regional expansions and intraspecific divergences are very common in most studied species during the Quaternary oscillations. Different intraspecific lineages or alleles (haplotypes) were detected in multiple localized refugia, from where regional or local expansions are likely to have started. Hybridizations and introgressions are frequent between intraspecific lineages or between different species. We also reviewed computational methods for phylogeographic analyses. Despite the great progress made in recent years, there remains much to discover about the spatial–temporal dimensions and underlying speciation mechanisms of Chinese plants. Phylogeographic studies represent a key knot that connects the genus phylogeny (macroevolution) and speciation and adaptation (microevolution). Therefore, we advocate that: (i) phylogeographic studies of plants in China should be directed to the closely related species or a monophyletic group (for example, a genus or a section) in the coming years; and (ii) population genetic data based on direct sequencing multiple loci, especially those from nuclear genome and statistical tests should be widely adopted and enforced. The recovered intraspecific divergences and phylogeographic patterns of multiple‐species may allow us to better understand the high plant diversity in China and set up concrete hypotheses for studying plant speciation and diversification mechanisms in this region.
As the highest and largest plateau in the world, the Qinghai–Tibet Plateau, with its numerous endemic species, is one of the important alpine biodiversity hotspots. Only recently have the ...evolutionary histories and underlying adaptations of these alpine plants become clear, through research mostly based on testable experiments and analyses. In this issue, we collected a total of 13 papers related to such aims. In addition, we selected a few published papers to highlight the major findings in the recent past. We also outlined the outlook and direction of future research.
Chemotherapy and radiotherapy predominantly improve the clinical outcomes of patients with human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC). Whether this superiority ...goes on when treated with immune checkpoint inhibitors is still unclear. This study sought to determine the predictive value and potential mechanisms of HPV status for the treatment of programmed cell death 1 (PD-1)/ligand 1(PD-L1) inhibitors. We conducted an integrated analysis of the relationships between HPV status and PD-L1, tumor mutation burden (TMB) and inflammation-related immune cells and molecules, based on the analysis of repository databases and resected HNSCC specimens. The pooled analysis of overall survival (OS) and objective response rate (ORR) suggested that HPV-positive patients benefited more from PD-1/PD-L1 inhibitors than HPV-negative patients (OS: hazard ratio (HR) = 0.71, p = 0.02; ORR: 21.9% vs 14.1%, odds ratio (OR) = 1.79, p = 0.01). Analysis of public databases and resected HNSCC specimens revealed that HPV status was independent of PD-L1 expression and TMB in HNSCC. However, HPV infection significantly increased T-cell infiltration, immune effector cell activation and the diversity of T-cell receptors. Notably, HPV-positivity correlated with increased immune cytolytic activity and a T-cell-inflamed gene expression profile. This work provides evidence that HPV status can be used to predict the effectiveness of PD-1 inhibitors in HNSCC, independently of PD-L1 expression and TMB, and probably results from an inflamed immune microenvironment induced by HPV infection.
Cervical spondylotic myelopathy (CSM) is a common cause of disability with few treatments. Aberrant mitochondrial dynamics play a crucial role in the pathogenesis of various neurodegenerative ...diseases. Thus, regulation of mitochondrial dynamics may offer therapeutic benefit for the treatment of CSM. Muscone, the active ingredient of an odoriferous animal product, exhibits anti‐inflammatory and neuroprotective effects for which the underlying mechanisms remain obscure. We hypothesized that muscone might ameliorate inflammatory responses and neuronal damage by regulating mitochondrial dynamics. To this end, the effects of muscone on a rat model of chronic cervical cord compression, as well as activated BV2 cells and injured neurons, were assessed. The results showed that muscone intervention improved motor function compared with vehicle‐treated rats. Indeed, muscone attenuated pro‐inflammatory cytokine expression, neuronal‐apoptosis indicators in the lesion area, and activation of the nod‐like receptor family pyrin domain‐containing 3 inflammasome, nuclear transcription factor‐κB, and dynamin‐related protein 1 in Iba1‐ and βIII‐tubulin‐labeled cells. Compared with vehicle‐treated rats, compression sites of muscone‐treated animals exhibited elongated mitochondrial morphologies in individual cell types and reduced reactive oxygen species. In vitro results indicated that muscone suppressed microglial activation and neuronal damage by regulating related‐inflammatory or apoptotic molecules. Moreover, muscone inhibited dynamin‐related protein 1 activation in activated BV2 cells and injured neurons, whereby it rescued mitochondrial fragmentation and reactive oxygen species production, which regulate a wide range of inflammatory and apoptotic molecules. Our findings reveal that muscone attenuates neuroinflammation and neuronal damage in rats with chronic cervical cord compression by regulating mitochondrial fission events, suggesting its promise for CSM therapy.
Cervical spondylotic myelopathy (CSM) is a common cause of disability with few treatments. Muscone, the ingredient from an animal product, exhibits anti‐inflammatory and neuroprotective effects for which the underlying mechanisms remain obscure. In this study, we explored the effects of muscone on a classic CSM rat model, microglial and neuronal cell. Results indicated that muscone could attenuate both inflammatory responses and neuronal damage in a rat CSM model and in vitro. Such effects may be associated with its role on mitochondrial dynamics and downstream signaling, suggesting that mitochondrial dynamics and muscone may be new highlights for the treatment of CSM.
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