Second People’s Hospital of Huai’an

Competing endogenous RNAs (ceRNAs) are transcripts that can regulate each other at post-transcription level by competing for shared miRNAs. CeRNA networks link the function of protein-coding mRNAs with that of non-coding RNAs such as microRNA, long non-coding RNA, pseudogenic RNA and circular RNA. Given that any transcripts harbouring miRNA response element can theoretically function as ceRNAs, they may represent a widespread form of post-transcriptional regulation of gene expression in both physiology and pathology. CeRNA activity is influenced by multiple factors such as the abundance and subcellular localisation of ceRNA components, binding affinity of miRNAs to their sponges, RNA editing, RNA secondary structures and RNA-binding proteins. Aberrations in these factors may deregulate ceRNA networks and thus lead to human diseases including cancer. In this review, we introduce the mechanisms and molecular bases of ceRNA networks, discuss their roles in the pathogenesis of cancer as well as methods of predicting and validating ceRNA interplay. At last, we discuss the limitations of current ceRNA theory, propose possible directions and envision the possibilities of ceRNAs as diagnostic biomarkers or therapeutic targets.

Quercetin is a kind of flavonoid compounds that comes from nature and is widely existed in the daily diet. Previous studies have found that quercetin has many effects such as anti-inflammatory, anti-oxidation and anti-cancer. Both in vivo and in vitro experiments have demonstrated that quercetin can exert anti-tumor effects by altering cell cycle progression, inhibiting cell proliferation, promoting apoptosis, inhibiting angiogenesis and metastasis progression, and affecting autophagy. This review summarizes the evidence for the pharmacological potential and inhibition of quercetin on cancers, supporting the viewpoint that quercetin should be adequately considered as a therapeutic agent against various cancers.

Polysaccharides are ideal natural resources for supplements and pharmaceuticals that have received more and more attention over the years. Natural polysaccharides have been shown to have fewer side effects, but because of their inherently physicochemical properties, their bioactivities were difficult to compare with those of synthetic drugs. Thus, researchers have modified the structures and properties of natural polysaccharides based on structure-activity relationships and have obtained better functionally improved polysaccharides. This review focuses on the major modification methods of polysaccharides, and discusses the effect of molecular modification on their physicochemical properties and bioactivities. Molecular modification methods mainly include chemical, physical, and biological changes. Chemical modification is the most widely used method; it can significantly increase the water solubility and bioactivities of polysaccharides by grafting onto other groups. Physical and biological modifications only change the molecular weight of a polysaccharide, and thereby change its physicochemical properties and bioactivities. Most of the molecular modifications bring about an increase in the antioxidant activity of polysaccharides, and among these, sulfated and acetylated modifications are very common. Furthermore, phosphorylation modification is the most common application to increase antitumor activity, and modified polysaccharides have been shown to have anti-HIV activity as the result of sulfated modification.

Immunogenic cell death (ICD) provides momentous theoretical principle for modern cancer immunotherapy. However, the currently available ICD inducers are still very limited and photosensitizer-based ones can hardly induce sufficient ICD to achieve satisfactory cancer immunotherapy by themselves. Herein, an organic photosensitizer (named TPE-DPA-TCyP) with a twisted molecular structure, strong aggregation-induced emission activity, and specific ability is reported for effectively inducing focused mitochondrial oxidative stress of cancer cells, which can serve as a much superior ICD inducer to the popularly used ones, including chlorin e6 (Ce6), pheophorbide A, and oxaliplatin. Furthermore, more effective in vivo ICD immunogenicity of TPE-DPA-TCyP than Ce6 is also demonstrated using a prophylactic tumor vaccination model. The underlying mechanism of the effectiveness and robustness of TPE-DPA-TCyP in inducing antitumor immunity and immune-memory effect in vivo is verified by immune cell analyses. This study thus reveals that inducing focused mitochondrial oxidative stress is a highly effective strategy to evoke abundant and large-scale ICD.

IMPORTANCE: Although the benefit of reducing blood pressure for primary and secondary prevention of stroke has been established, the effect of antihypertensive treatment in patients with acute ischemic stroke is uncertain. OBJECTIVE: To evaluate whether immediate blood pressure reduction in patients with acute ischemic stroke would reduce death and major disability at 14 days or hospital discharge. DESIGN, SETTING, AND PARTICIPANTS: The China Antihypertensive Trial in Acute Ischemic Stroke, a single-blind, blinded end-points randomized clinical trial, conducted among 4071 patients with nonthrombolysed ischemic stroke within 48 hours of onset and elevated systolic blood pressure. Patients were recruited from 26 hospitals across China between August 2009 and May 2013. INTERVENTIONS: Patients (n = 2038) were randomly assigned to receive antihypertensive treatment (aimed at lowering systolic blood pressure by 10% to 25% within the first 24 hours after randomization, achieving blood pressure less than 140/90 mm Hg within 7 days, and maintaining this level during hospitalization) or to discontinue all antihypertensive medications (control) during hospitalization (n = 2033). MAIN OUTCOMES AND MEASURES: Primary outcome was a combination of death and major disability (modified Rankin Scale score ≥3) at 14 days or hospital discharge. RESULTS: Mean systolic blood pressure was reduced from 166.7 mm Hg to 144.7 mm Hg (-12.7%) within 24 hours in the antihypertensive treatment group and from 165.6 mm Hg to 152.9 mm Hg (-7.2%) in the control group within 24 hours after randomization (difference, -5.5% [95% CI, -4.9 to -6.1%]; absolute difference, -9.1 mm Hg [95% CI, -10.2 to -8.1]; P < .001). Mean systolic blood pressure was 137.3 mm Hg in the antihypertensive treatment group and 146.5 mm Hg in the control group at day 7 after randomization (difference, -9.3 mm Hg [95% CI, -10.1 to -8.4]; P < .001). The primary outcome did not differ between treatment groups (683 events [antihypertensive treatment] vs 681 events [control]; odds ratio, 1.00 [95% CI, 0.88 to 1.14]; P = .98) at 14 days or hospital discharge. The secondary composite outcome of death and major disability at 3-month posttreatment follow-up did not differ between treatment groups (500 events [antihypertensive treatment] vs 502 events [control]; odds ratio, 0.99 [95% CI, 0.86 to 1.15]; P = .93). CONCLUSION AND RELEVANCE: Among patients with acute ischemic stroke, blood pressure reduction with antihypertensive medications, compared with the absence of hypertensive medication, did not reduce the likelihood of death and major disability at 14 days or hospital discharge. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01840072.

BACKGROUND: loss-of-function carriers have not been extensively performed. METHODS: loss-of-function alleles. Patients were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive ticagrelor (180 mg on day 1 followed by 90 mg twice daily on days 2 through 90) and placebo clopidogrel or to receive clopidogrel (300 mg on day 1 followed by 75 mg once daily on days 2 through 90) and placebo ticagrelor; both groups received aspirin for 21 days. The primary efficacy outcome was new stroke, and the primary safety outcome was severe or moderate bleeding, both within 90 days. RESULTS: A total of 11,255 patients were screened and 6412 patients were enrolled, with 3205 assigned to the ticagrelor group and 3207 to the clopidogrel group. The median age of the patients was 64.8 years, and 33.8% were women; 98.0% belonged to the Han Chinese ethnic group. Stroke occurred within 90 days in 191 patients (6.0%) in the ticagrelor group and 243 patients (7.6%) in the clopidogrel group (hazard ratio, 0.77; 95% confidence interval, 0.64 to 0.94; P = 0.008). Secondary outcomes were generally in the same direction as the primary outcome. Severe or moderate bleeding occurred in 9 patients (0.3%) in the ticagrelor group and in 11 patients (0.3%) in the clopidogrel group; any bleeding occurred in 170 patients (5.3%) and 80 patients (2.5%), respectively. CONCLUSIONS: loss-of-function alleles, the risk of stroke at 90 days was modestly lower with ticagrelor than with clopidogrel. The risk of severe or moderate bleeding did not differ between the two treatment groups, but ticagrelor was associated with more total bleeding events than clopidogrel. (Funded by the Ministry of Science and Technology of the People's Republic of China and others; CHANCE-2 ClinicalTrials.gov number, NCT04078737.).

Importance: Several randomized clinical trials have recently established the safety and efficacy of endovascular treatment (EVT) of acute ischemic stroke in the anterior circulation. However, it remains uncertain whether patients with acute basilar artery occlusion (BAO) benefit from EVT. Objective: To evaluate the association between EVT and clinical outcomes of patients with acute BAO. Design, Setting, and Participants: This nonrandomized cohort study, the EVT for Acute Basilar Artery Occlusion Study (BASILAR) study, was a nationwide prospective registry of consecutive patients presenting with an acute, symptomatic, radiologically confirmed BAO to 47 comprehensive stroke centers across 15 provinces in China between January 2014 and May 2019. Patients with acute BAO within 24 hours of estimated occlusion time were divided into groups receiving standard medical treatment plus EVT or standard medical treatment alone. Main Outcomes and Measures: The primary outcome was the improvement in modified Rankin Scale scores (range, 0 to 6 points, with higher scores indicating greater disability) at 90 days across the 2 groups assessed as a common odds ratio using ordinal logistic regression shift analysis, adjusted for prespecified prognostic factors. The secondary efficacy outcome was the rate of favorable functional outcomes defined as modified Rankin Scale scores of 3 or less (indicating an ability to walk unassisted) at 90 days. Safety outcomes included symptomatic intracerebral hemorrhage and 90-day mortality. Results: A total of 1254 patients were assessed, and 829 patients (of whom 612 were men [73.8%]; median [interquartile] age, 65 [57-74] years) were recruited into the study. Of these, 647 were treated with standard medical treatment plus EVT and 182 with standard medical treatment alone. Ninety-day functional outcomes were substantially improved by EVT (adjusted common odds ratio, 3.08 [95% CI, 2.09-4.55]; P < .001). Moreover, EVT was associated with a significantly higher rate of 90-day modified Rankin Scale scores of 3 or less (adjusted odds ratio, 4.70 [95% CI, 2.53-8.75]; P < .001) and a lower rate of 90-day mortality (adjusted odds ratio, 2.93 [95% CI, 1.95-4.40]; P < .001) despite an increase in symptomatic intracerebral hemorrhage (45 of 636 patients [7.1%] vs 1 of 182 patients [0.5%]; P < .001). Conclusions and Relevance: Among patients with acute BAO, EVT administered within 24 hours of estimated occlusion time is associated with better functional outcomes and reduced mortality.

In cancer, T cells become dysfunctional owing to persistent antigen exposure. Dysfunctional T cells are characterized by reduced proliferative capacity, decreased effector function, and overexpression of multiple inhibitory receptors. Due to the presence of various inhibitory signals in the complex tumor microenvironment, tumor-specific T cells have distinct dysfunction states. Therapeutic reactivation of tumor-specific T cells has yielded good results in cancer patients. Here, we review the hallmarks of T cell dysfunction in cancer. Also, we discuss the relationship between T cell dysfunction and cancer immunotherapy.

BACKGROUND/AIMS: Mounting evidence suggests that epitranscriptional modifications regulate multiple cellular processes. N6-Methyladenosine (m6A), the most abundant reversible methylation of mRNA, has critical roles in cancer pathogenesis. However, the mechanisms and functions of long non-coding RNA (lncRNA) methylation remain unclear. Pancreatic cancer resulted in 411,600 deaths globally in 2015. By the time of pancreatic cancer diagnosis, metastasis has often occurred in other parts of the body. The present study sought to investigate lncRNA m6A modification and its roles in pancreatic cancer. METHODS: Differential expression between cancer cells and matched normal cells was evaluated to identify candidate lncRNAs. The lncRNA KCNK15-AS1 was detected in cancer tissues and various pancreatic cells using RT-qPCR. KCNK15-AS1 was transfected into cells to explore its role in migration and invasion. Then, m6A RNA immunoprecipitation was performed to detect methylated KCNK15-AS1 in tissues and cells. Epithelial-mesenchymal transition (EMT) markers were used to evaluate KCNK15-AS1-mediated EMT processes. RESULTS: KCNK15-AS1 was downregulated in pancreatic cancer tissues compared with paired adjacent normal tissues. KCNK15-AS1 inhibited migration and invasion in MIA PaCa-2 and BxPC-3 cells. Furthermore, total RNA methylation in cancer cells was significantly enriched relative to that in immortalized human pancreatic duct epithelial (HPDE6-C7) cells. In addition, the m6A eraser ALKBH5 was downregulated in cancer cells, which can demethylate KCNK15-AS1 and regulate KCNK15-AS1-mediated cell motility. CONCLUSION: Our results have revealed a novel mechanism by which ALKBH5 inhibits pancreatic cancer motility by demethylating lncRNA KCNK15-AS1, identifying a potential therapeutic target for pancreatic cancer.

Limited data are available for clinical characteristics of patients with coronavirus disease 2019 (COVID-19) outside Wuhan. This study aimed to describe the clinical characteristics of COVID-19 and identify the risk factors for severe illness of COVID-19 in Jiangsu province, China. Clinical data of hospitalized COVID-19 patients were retrospectively collected in 8 hospitals from 8 cities of Jiangsu province, China. Clinical findings of COVID-19 patients were described and risk factors for severe illness of COVID-19 were analyzed. By Feb 10, 2020, 202 hospitalized patients with COVID-19 were enrolled. The median age of patients was 44.0 years (interquartile range, 33.0-54.0). 55 (27.2%) patients had comorbidities. At the onset of illness, the common symptoms were fever (156 [77.2%]) and cough (120 [59.4%]). 66 (32.7%) patients had lymphopenia. 193 (95.5%) patients had abnormal radiological findings. 11 (5.4%) patients were admitted to the intensive care unit and none of the patients died. 23 (11.4%) patients had severe illness. Severe illness of COVID-19 was independently associated with body mass index (BMI) ≥ 28 kg/m2 (odds ratio [OR], 9.219; 95% confidence interval [CI], 2.731 to 31.126; P<0.001) and a known history of type 2 diabetes (OR, 4.326; 95% CI, 1.059 to 17.668; P = 0.041). In this case series in Jiangsu Province, COVID-19 patients had less severe symptoms and had better outcomes than the initial COVID-19 patients in Wuhan. The BMI ≥ 28 kg/m2 and a known history of type 2 diabetes were independent risk factors of severe illness in patients with COVID-19.

Abstract Background As one of the main functional forms of mesenchymal stem cells (MSCs), MSC-derived extracellular vesicles (MSC-EVs) have shown an alternative therapeutic option in experimental models of allergic asthma. Oxygen concentration plays an important role in the self-renewal, proliferation, and EV release of MSCs and a recent study found that the anti-asthma effect of MSCs was enhanced by culture in hypoxic conditions. However, the potential of hypoxic MSC-derived EVs (Hypo-EVs) in asthma is still unknown. Methods BALB/c female mice were sensitized and challenged with ovalbumin (OVA), and each group received PBS, normoxic human umbilical cord MSC-EVs (Nor-EVs), or Hypo-EVs weekly. After treatment, the animals were euthanized, and their lungs and bronchoalveolar lavage fluid (BALF) were collected. With the use of hematoxylin and eosin (HE), periodic acid-Schiff (PAS) and Masson’s trichrome staining, enzyme-linked immune sorbent assay (ELISA), Western blot analysis, and real-time PCR, the inflammation and collagen fiber content of airways and lung parenchyma were investigated. Results Hypoxic environment can promote human umbilical cord MSCs (hUCMSCs) to release more EVs. In OVA animals, the administration of Nor-EVs or Hypo-EVs significantly ameliorated the BALF total cells, eosinophils, and pro-inflammatory mediators (IL-4 and IL-13) in asthmatic mice. Moreover, Hypo-EVs were generally more potent than Nor-EVs in suppressing airway inflammation in asthmatic mice. Compared with Nor-EVs, Hypo-EVs further prevented mouse chronic allergic airway remodeling, concomitant with the decreased expression of pro-fibrogenic markers α-smooth muscle actin (α-SMA), collagen-1, and TGF-β1-p-smad2/3 signaling pathway. In vitro, Hypo-EVs decreased the expression of p-smad2/3, α-SMA, and collagen-1 in HLF-1 cells (human lung fibroblasts) stimulated by TGF-β1. In addition, we showed that miR-146a-5p was enriched in Hypo-EVs compared with that in Nor-EVs, and Hypo-EV administration unregulated the miR-146a-5p expression both in asthma mice lung tissues and in TGF-β1-treated HLF-1. More importantly, decreased miR-146a-5p expression in Hypo-EVs impaired Hypo-EV-mediated lung protection in OVA mice. Conclusion Our findings provided the first evidence that hypoxic hUCMSC-derived EVs attenuated allergic airway inflammation and airway remodeling in chronic asthma mice, potentially creating new avenues for the treatment of asthma.

A straightforward approach is developed for fabrication of a visible-light-driven Ag/g-C3N4 catalyst. Morphological observation shows that the g-C3N4 sheets are decorated with highly dispersed Ag nanoparticles having an average size of 5.6 nm. The photocatalytic activity measurements demonstrate that the photocatalytic degradation rates of methyl orange (MO), methylene blue (MB), and neutral dark yellow GL (NDY-GL) over Ag/g-C3N4-4 can reach up to 98.2, 99.3 and 99.6% in the presence of borohydride ions (BH4(-)) only with 8, 45, and 16 min visible light irradiation, respectively. The significant enhancement in photoactivity of the catalyst is mainly attributed to the high dispersity and smaller size of Ag nanoparticles, the strong surface plasmon resonance (SPR) effect of metallic Ag nanoparticles, the efficient separation of photogenerated charge carriers, the additional superoxide radicals (O) generated from the reduction of dissolved oxygen in the presence of BH4(-) and the synergistic effect of Ag nanoparticles and g-C3N4.

Exosomes derived from lung cancer cells confer cisplatin (DDP) resistance to other cancer cells. However, the underlying mechanism is still unknown. A549 resistance to DDP (A549/DDP) was established. Microarray was used to analyze microRNA (miRNA) expression profiles of A549 cells, A549/DDP cells, A549 exosomes, and A549/DDP exosomes. There was a strong correlation of miRNA profiles between exosomes and their maternal cells. A total of 11 miRNAs were significantly upregulated both in A549/DDP cells compared with A549 cells and in exosomes derived from A549/DDP cells in contrast to exosomes from A549 cells. A total of 31 downregulated miRNAs were also observed. miR-100-5p was the most prominent decreased miRNA in DDP-resistant exosomes compared with the corresponding sensitive ones. Downregulated miR-100-5p was proved to be involved in DDP resistance in A549 cells, and mammalian target of rapamycin (mTOR) expression was reverse regulated by miR-100-5p. Exosomes confer recipient cells' resistance to DDP in an exosomal miR-100-5p-dependent manner with mTOR as its potential target both in vitro and in vivo. Exosomes from DDP-resistant lung cancer cells A549 can alter other lung cancer cells' sensitivity to DDP in exosomal miR-100-5p-dependent manner. Our study provides new insights into the molecular mechanism of DDP resistance in lung cancer.

China, as the one of the largest developing countries in the world and with about one-fifth of the global population, is bearing an increasing burden on health from cancer. In the area of esophageal cancer (EC), China accounts for more than 50% of the global cases, with this disease being a particularly worse for those in disadvantaged populations. Along with China's socioeconomic condition, the epidemiology, diagnosis, therapeutics and research of EC have developed throughout the 21st century. In the current review, existing control measures for EC in China are outlined, including the incidence, mortality, screening, clinical diagnosis, multidisciplinary treatment and research landscape. EC in China are very different from those in some other parts of the world, especially in Western countries. Core measures that could contribute to the prevention of EC and improve clinical outcomes in patients of less developed countries and beyond are recommended. International cooperation among academia, government and industry is especially warranted in global EC control.

BACKGROUND: Inflammation plays an integral role in carcinogenesis and tumor progression. Inflammatory response biomarkers have shown to be promising prognostic factors for improving the predictive accuracy in various cancers. The aim of this study is to investigate the prognostic significance of pre-operative neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR) in gastric cancer (GC). METHODS: 389 patients who had undergone gastrectomy were enrolled from 2007 to 2009 in this study. NLR, dNLR, PLR and LMR were calculated from peripheral blood cell count taken at pre-operation. Receiver operating curve (ROC) was used to determine the optimal cut-off levels for these biomarkers. A predictive model or nomogram was established to predict prognosis for cancer-specific survival (CSS) and disease-free survival (DFS), and the predictive accuracy of the nomogram was determined by concordance index (c-index). RESULTS: The median follow-up period was 24 months ranging from 3 months to 60 months. The optimal cut-off levels were 2.36 for NLR, 1.85 for dNLR, 132 for PLR and 4.95 for LMR by ROC curves analysis. Elevated NLR, dNLR and PLR were significantly associated with worse overall survival (OS), CSS and DFS, however, elevated LMR showed an adverse effect on worse OS, CSS and DFS. Multivariate analysis revealed that elevated dNLR was an independent factor for worse OS, and NLR was superior to dNLR, PLR and LMR in terms of hazard ratio (HR = 1.53, 95% CI = 1.11-2.11, P = 0.010), which was shown to be independent prognostic indicators for both CSS and DFS. Moreover, the nomogram could more accurately predict CSS (c-index: 0.89) and DFS (c-index: 0.84) in surgical GC patients. CONCLUSIONS: Pre-operative NLR and dNLR may serve as potential prognostic biomarkers in patients with GC who underwent surgical resection. The proposed nomograms can be used for the prediction of CSS and DFS in patients with GC who have undergone gastrectomy.

First introduced into mammalian organisms in 2013, the RNA-guided genome editing tool CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9) offers several advantages over conventional ones, such as simple-to-design, easy-to-use and multiplexing (capable of editing multiple genes simultaneously). Consequently, it has become a cost-effective and convenient tool for various genome editing purposes including gene therapy studies. In cell lines or animal models, CRISPR-Cas9 can be applied for therapeutic purposes in several ways. It can correct the causal mutations in monogenic disorders and thus rescue the disease phenotypes, which currently represents the most translatable field in CRISPR-Cas9-mediated gene therapy. CRISPR-Cas9 can also engineer pathogen genome such as HIV for therapeutic purposes, or induce protective or therapeutic mutations in host tissues. Moreover, CRISPR-Cas9 has shown potentials in cancer gene therapy such as deactivating oncogenic virus and inducing oncosuppressor expressions. Herein, we review the research on CRISPR-mediated gene therapy, discuss its advantages, limitations and possible solutions, and propose directions for future research, with an emphasis on the opportunities and challenges of CRISPR-Cas9 in cancer gene therapy.

Metal-organic frameworks (MOFs) have emerged as attractive materials for energy and environmental-related applications owing to their structural, chemical and functional diversity over the last two decades. It is known that the poor carrier mobility and low electrical conductivity of ordinary MOFs severely limit their utility in practical applications. In the past 10 years, several MOF materials with high carrier mobility and outstanding electrical conductivity have received a worldwide upsurge of research interest and many techniques and strategies have been used to synthesize such MOFs. In this critical review, we provide an overview of the significant advances in the development of conductive MOFs reported until now. Their theoretical and synthetic design strategies, conductive mechanisms, electrical transport measurements, and applications are systematically summarized and discussed. In addition, we will also give some discussions on challenges and perspectives in this exciting field.

The cell cycle regulator p16 is known as a biomarker and an effector of aging. However, its function in intervertebral disc degeneration (IVDD) is unclear. In this study, p16 expression levels were found to be positively correlated with the severity of human IVDD. In a mouse tail suspension (TS)-induced IVDD model, lumbar intervertebral disc height index and matrix protein expression levels were reduced significantly were largely rescued by p16 deletion. In TS mouse discs, reactive oxygen species levels, proportions of senescent cells, and the senescence-associated secretory phenotype (SASP) were all increased, cell cycling was delayed, and expression was downregulated for Sirt1, superoxide dismutase 1/2, cyclin-dependent kinases 4/6, phosphorylated retinoblastoma protein, and transcription factor E2F1/2. However, these effects were rescued by p16 deletion. Our results demonstrate that p16 plays an important role in IVDD pathogenesis and that its deletion attenuates IVDD by promoting cell cycle and inhibiting SASP, cell senescence, and oxidative stress.

Understanding the mechanism and progression of neutrophil-involved diseases (e.g., acute inflammation) is of great importance. However, current available analytical methods neither achieve the real-time monitoring nor provide dynamic information during the pathological processes. Herein, a peroxynitrite (ONOO–) and environmental pH dual-responsive afterglow luminescent nanoprobe is designed and synthesized. In the presence of ONOO– at physiological pH, the nanoprobes show activated near-infrared afterglow luminescence, whose intensity and lasting time can be highly enhanced by introducing the aggregation-induced emission (AIE) effect with a twisted molecular geometry into the system. In vivo studies using three diseased animal models demonstrate that the nanoprobes can sensitively reveal the development process of acute skin inflammation including infiltration of first arrived neutrophils and acidification initiating time, make a fast and accurate discrimination between allergy and inflammation, and rapidly screen the antitumor drugs capable of inducing immunogenic cell death. This work provides an alternative approach and advanced probes permitting precise disease monitoring in real time.

Recent studies have exhibited significant roles of lncRNAs in various tumors' development, including colon cancer. Our study focused on the biological roles of lncRNA MALAT1 in colon cancer. In our study, it was demonstrated that MALAT1 was upregulated in human colon cancer cell lines including Lovo, HCT116, SW480, and HT29 cells compared to the normal human intestinal epithelial HIEC cells. Moreover, we observed that miR-129-5p was downregulated in colon cancer cells with a significant increase of HMGB1 expression. Inhibition of MALAT1 can inhibit the proliferation of colon cancer SW480 and HCT116 cells and next, bioinformatics analysis was used to predict the target microRNA of MALAT1. miR-129-5p was identified and confirmed as a direct regulator of MALAT1 and it was shown that miR-129-5p mimics were able to restrain the progression of colon cancer cells. In addition, high motility group box protein 1 (HMGB1), was predicted as a mRNA target of miR-129-5p. Furthermore, we found that MALAT1 exerted its biological functions through regulating HMGB1 by sponging miR-129-5p in vitro. Silencing MALAT1 greatly inhibited HMGB1 expression which can be reversed by miR-129-5p inhibitors. It was indicated in our investigation that MALAT1 may serve as a competing endogenous lncRNA (ceRNA) to mediate HMGB1 by sponging miR-129-5p in colon cancer. Taken together, our results indicated that MALAT1/miR-129-5p/HMGB1 axis could be provided as an important prognostic biomarker in colon cancer development.