ABSTRACT Background: The efficacy of neoadjuvant therapy for rectal cancer has not been assessed. Objective: To evaluate proportional changes in peripheral blood immune cells in rectal cancer ...patients after neoadjuvant therapy and assess the relationship between tumor regression and regulatory T (Treg) cells. Materials and Methods: Rectal cancer patients who had received neoadjuvant therapy prior to surgery at Shanxi Cancer Hospital between January and September 2018 were enrolled in the study. Treg, CD4 + T, CD8 + T, NK, B cells, and CD4 + /CD8+ ratio in peripheral blood before and after neoadjuvant therapy were measured by flow cytometry. Patients were divided into down-staging and control groups, depending on their responses to neoadjuvant therapy. Results: A total of 108 patients were enrolled. The proportion of Treg cells was significantly lower after neoadjuvant therapy ( P < 0.05) but no changes were seen in CD4 + T, CD8 + T, NK, B cells, or CD4 + /CD8 + ratio (all P > 0.05). There were 76 patients in the down-staging and 32 in the control groups. There were no significant differences in clinical parameters between down-staging and control groups (all P > 0.05). There were no significant differences in immune cell proportions between the two groups prior to neoadjuvant therapy (all P > 0.05). Treg, CD4 + T, and B cells were all significantly lower in the down-staging group after neoadjuvant therapy than before ( P < 0.05). CD4 + /CD8 + ratios were lower ( P < 0.05) while proportions of Treg and natural killer (NK) cells did not change after neoadjuvant therapy in the control group. Following neoadjuvant therapy, Treg and B cells were lower while CD4 + and CD4 + /CD8 + ratios were higher in the down-staging group compared to the control group ( P < 0.01). Conclusion: Treg cells may constitute a reference for judging the effect of neoadjuvant therapy in rectal cancer patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Colorectal cancer (CRC) is one of the most common digestive malignant tumors globally. Focally amplified lncRNA on chromosome 1 (FALEC) is a novel lncRNA that has been reported to be involved in many ...biological processes during carcinogenesis. However, its role in CRC remains poorly understood.
Gene expression at mRNA or protein level was measured by qRT-PCR or western blot, respectively. In vitro experiments including EdU, colony formation, flow cytometry, wound-healing and transwell assays, as well as in vivo xenograft experiment, were utilized to determine the functional role of FALEC in CRC. Relevant mechanical assays were performed to investigate the underlying molecular mechanism.
FALEC was aberrantly up-regulated in CRC. FALEC knockdown could impair CRC cell proliferation, migration and invasion, whereas facilitate cell apoptosis. MiR-2116-3p was revealed to be sponged by FALEC. PIWIL1 was identified as the target of miR-2116-3p. Mechanically, FALEC restored the expression of PIWIL1 via absorbing miR-2116-3p. MiR-2116-3p inhibition and PIWIL1 enrichment could counteract the anti-tumor impact induced by silenced FALEC on the oncogenic behaviors of CRC cells.
Our study revealed that FALEC promoted CRC progression via restoring the expression of miR-2116-3p-targeted PIWIL1, suggesting the potential application of targeting FALEC in the treatment of CRC.
Pregnant women are generally more susceptible to viral infection. Although the impact of SARS-CoV-2 on pregnant women remains to be determined, evidence indicates that risks of adverse clinical ...outcomes are similar in pregnancy to the general population. Here we analyzed clinical symptoms and outcomes of 20 pregnant and 299 reproductive-aged non-pregnant female COVID-19 patients who were hospitalized during the same period. Laboratory measurements were compared among mild cases and healthy pregnant women. Our study found that pregnant patients showed enhanced innate immune response evident by higher neutrophils and C-reactive protein. Cytokines, chemokines, and growth factors (CCGFs) profiles from 11 pregnant and 4 non-pregnant COVID-19 patients and 10 healthy pregnant female patients, and lymphocyte subsets analysis of 7 pregnant patients and 19 non-pregnant patients, indicate suppressed cytokine storm and potential enhanced CD8+ T cell and NK cell activity in pregnant patients with COVID-19, which may be essential in contributing to the unique anti-SARS-CoV-2 response in pregnancy.
A 2-(2'-hydroxyphenyl)benzimidazole (HBI)-based ratiometric fluorescent probe, known as BTEP, was synthesized using 5-bromosalicylaldehyde as the raw material
Sonogashira coupling and condensation ...reaction. This probe was designed for rapid detection of boron trifluoride solutions and gases. The N and O coordination atoms in the probe undergo a boron difluoride addition with BF
, which affects the process of excited state intramolecular proton transfer (ESIPT) leading to a blue shift of fluorescence emission. Obvious changes in the fluorescence signal can be observed within 60 seconds. The introduction of an acetylene trimethylsilane fragment increases the conjugate plane and is beneficial to improving the selectivity of the probe. The
/
fluorescence ratio of the probe displays a linear relationship with the concentration of BF
in the range of 5-50 μM, with a detection of limit as low as 69.5 nM. Furthermore, the probe demonstrates specific and selective recognition of BF
among eight common interference substances. Test strips prepared using BTEP have the capability of real-time naked-eye detection of trace BF
gas.
Utilizing statistical information from the Seventh National Population Census, statistical yearbook and sampling dynamic survey data, this study examines the distribution characteristics of the ...floating population in Beijing, Tianjin and Hebei Region as well as the growth trend of the floating population in each region. It also makes assessments using floating population concentration and The Moran Index Computing Methods. According to the study, the spatial distribution of the floating population has a clear clustering pattern in Beijing, Tianjin and Hebei region. Beijing, Tianjin and Hebei region's mobile population growth patterns differ substantially, and the region's inflow population is mostly made up of migrant inhabitants of domestic provinces and inflow of people from nearby regions. Most of the mobile population resides in Beijing and Tianjin, whereas the outflow of people originates in Hebei province. The diffusion impact and the spatial features of the floating population in the Beijing, Tianjin and Hebei area have a constant, positive association, according to the timeline between 2014 and 2020.
•L1 and L2 processing in late bilinguals could be captured by brain dynamic states.•Distinct brain state dynamics were found in L1 and L2 processing in late bilinguals.•L1 processing was associated ...with more integrated states and greater transition flexibility.•L2 processing was associated with more segregated states and insufficient transition flexibility.
The process of complex cognition, which includes language processing, is dynamic in nature and involves various network modes or cognitive modes. This dynamic process can be manifested by a set of brain states and transitions between them. Previous neuroimaging studies have shed light on how bilingual brains support native language (L1) and second language (L2) through a shared network. However, the mechanism through which this shared brain network enables L1 and L2 processing remains unknown. This study examined this issue by testing the hypothesis that L1 and L2 processing is associated with distinct brain state dynamics in terms of brain state integration and transition flexibility. A group of late Chinese-English bilinguals was scanned using functional magnetic resonance imaging (fMRI) while listening to eight short narratives in Chinese (L1) and English (L2). Brain state dynamics were modeled using the leading eigenvector dynamic analysis framework. The results show that L1 processing involves more integrated states and frequent transitions between integrated and segregated states, while L2 processing involves more segregated states and fewer transitions. Our work provides insight into the dynamic process of narrative listening comprehension in late bilinguals and sheds new light on the neural representation of language processing and related disorders.
Radish (
L.) is an economically important vegetable worldwide, but its sustainable production and breeding are highly threatened by blight disease caused by
. Melatonin is an important growth ...regulator that can influence physiological activities in both plants and microbes and stimulate biotic stress resistance in plants. In this study, 0-1500 μM melatonin was exogenously applied to healthy radish seedlings,
incubated
, and diseased radish seedlings to determine the effects of melatonin on host, pathogen, and host-pathogen interaction. At sufficient concentrations (0-500 μM), melatonin enhanced growth and immunity of healthy radish seedlings by improving the function of organelles and promoting the biosynthesis of antioxidant enzymes, chitin, organic acid, and defense proteins. Interestingly, melatonin also improved colony growth, development, and virulence of
. A strong dosage-dependent effect of melatonin was observed: 50-500 μM promoted host and pathogen vitality and resistance (500 μM was optimal) and 1500 μM inhibited these processes. Significantly less blight was observed on diseased seedlings treated with 500 μM melatonin, indicating that melatonin more strongly enhanced the growth and immunity of radish than it promoted the development and virulence of
at this treatment concentration. These effects of MT were mediated by transcriptional changes of key genes as identified by RNA-seq, Dual RNA-seq, and qRT-PCR. The results from this work provide a theoretical basis for the application of melatonin to protect vegetable crops against pathogens.
Fueled by the development of neuroscience and artificial intelligence (AI), recent advances in the brain-inspired AI have manifested a tipping-point in the collaboration of the two fields. AI began ...with the inspiration of neuroscience, but has evolved to achieve a remarkable performance with little dependence upon neuroscience. However, in a recent collaboration, research into neurobiological explainability of AI models found that these highly accurate models may resemble the neurobiological representation of the same computational processes in the brain, although these models have been developed in the absence of such neuroscientific references. In this perspective, we review the cooperation and separation between neuroscience and AI, and emphasize on the current advance, that is, a new cooperation, the neurobiological explainability of AI. Under the intertwined development of the two fields, we propose a practical framework to evaluate the brain-likeness of AI models, paving the way for their further improvements.
Abstract Background Colorectal cancer (CRC) metachronous liver metastasis is a significant clinical challenge, largely attributable to the late detection and the intricate molecular mechanisms that ...remain poorly understood. This study aims to elucidate the role of Solute Carrier Family 14 Member 1 (SLC14A1) in the pathogenesis and progression of CRC metachronous liver metastasis. Methods We conducted a comprehensive analysis of CRC patient data from The Cancer Genome Atlas and GSE40967 databases, focusing on the differential expression of genes associated with non-metachronous liver metastasis and metachronous liver metastasis. Functional assays, both in vitro and in vivo, were performed to assess the biological impact of SLC14A1 modulation in CRC cells. Gene set enrichment analysis, molecular assays and immunohistochemical analyses on clinical specimens were employed to unravel the underlying mechanisms through which SLC14A1 exerts its effects. Results SLC14A1 was identified as a differentially expressed gene, with its overexpression significantly correlating with poor relapse-free and overall survival. Mechanistically, elevated SLC14A1 levels enhanced CRC cell invasiveness and migratory abilities, corroborated by upregulated TGF-β/Smad signaling and Epithelial-Mesenchymal Transition. SLC14A1 interacted with TβRII and stabilized TβRII protein, impeding its Smurf1-mediated K48-linked ubiquitination and degradation, amplifying TGF-β/Smad signaling. Furthermore, TGF-β1 reciprocally elevated SLC14A1 mRNA expression, with Snail identified as a transcriptional regulator, binding downstream of SLC14A1’s transcription start site, establishing a positive feedback loop. Clinically, SLC14A1, phosphorylated Smad2, and Snail were markedly upregulated in CRC patients with metachronous liver metastasis, underscoring their potential as prognostic markers. Conclusions Our findings unveil SLC14A1 as a critical regulator in CRC metachronous liver metastasis, providing novel insights into the molecular crosstalk between SLC14A1 and TGF-β/Smad signaling. These discoveries not only enhance our understanding of CRC metachronous liver metastasis pathogenesis, but also highlight SLC14A1 as a promising target for therapeutic intervention and predictive marker.
•We found greater activation in the LIPL in L2 processing than in L1 processing.•Association of the LIPL and L2 was mainly observed in the phonological task.•Functional plasticity of the LIPL was ...elicited by phonological-based training.•Preference of the LIPL to L2 may link with its role in phonological processing.
Additional neural substance for reading in a second language has been reported by prior studies. However, to date, there has been little investigation into whether and how the brain's adaptation to a second language is induced by specific linguistic tasks or is a general effect during reading in a new language. To address this issue, our study investigated Chinese children learning English as a second language by combining cross-sectional and longitudinal Functional Magnetic Resonance Imaging (fMRI) studies. We compared brain activation across four reading tasks, orthographic tasks and phonological tasks in Chinese (the first language, L1) and English (the second language, L2). By comparing the activation pattern across languages, we observed greater activation in the left inferior parietal lobule (LIPL) in English compared to Chinese, suggesting a functional preference of the LIPL to L2. In addition, greater correlation between LIPL-related FC and L2 was mainly observed in the phonological task, indicating that LIPL could be associated with phonological processing. Moreover, a proportion of the children were enrolled in an 8-week phonological-based reading-training program. We observed significant functional plasticity of the LIPL elicited by this training program only in the English phonological task and not in the orthographic task, further substantiating that the additional requirements of the LIPL in L2 are mainly associated with phonological processing. The findings provide new insights into understanding the functional contribution of the LIPL to reading in a second language.
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