Summary Background MicroRNAs (miRNAs) can be used as prognostic biomarkers in many types of cancer. We aimed to identify miRNAs that were prognostic in patients with nasopharyngeal carcinoma. Methods ...We retrospectively analysed miRNA expression profiles in 312 paraffin-embedded specimens of nasopharyngeal carcinoma from Sun Yat-sen University Cancer Center (Guangzhou, China) and 18 specimens of non-cancer nasopharyngitis. Using an 873 probe microarray, we assessed associations between miRNA signatures and clinical outcome in a randomly selected 156 samples (training set) and validated findings in the remaining 156 samples (internal validation set). We confirmed the miRNAs signature using quantitative RT-PCR analysis in 156 samples from a second randomisation of the 312 samples, and validated the miRNA signature in 153 samples from the West China Hospital of Sichuan University in Chengdu, China (independent set). We used the Kaplan-Meier method and log-rank tests to estimate correlations of the miRNA signature with disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival. Findings 41 miRNAs were differentially expressed between nasopharyngeal carcinoma and non-cancer nasopharyngitis tissues. A signature of five miRNAs, each significantly associated with DFS, was identified in the training set. We calculated a risk score from the signature and classified patients as high risk or low risk. Compared with patients with low-risk scores, patients with high risk scores in the training set had shorter DFS (hazard ratio HR 2·73, 95% CI 1·46–5·11; p=0·0019), DMFS (3·48, 1·57–7·75; p=0·0020), and overall survival (2·48, 1·24–4·96; p=0·010). We noted equivalent findings in the internal validation set for DFS (2·47, 1·32–4·61; p=0·0052), DMFS (2·28, 1·09–4·80; p=0·030), and overall survival (2·87, 1·38–5·96; p=0·0051) and in the independent set for DFS (3·16, 1·65–6·04; p=0·0011), DMFS (2·39, 1·05–5·42; p=0·037), and overall survival (3·07, 1·34–7·01; p=0·0082). The five-miRNA signature was an independent prognostic factor. A combination of this signature and TNM stage had better prognostic value than did TNM stage alone in the training set (area under receiver operating characteristics 0·68 95% CI 0·60–0·76 vs 0·60 0·52–0·67; p=0·013), the internal validation set (0·70 0·61–0·78 vs 0·61 0·54–0·68; p=0·012), and the independent set (0·70 0·62–0·78 vs 0·63 0·56–0·69; p=0·032). Interpretation Identification of patients with the five-miRNA signature might add prognostic value to the TNM staging system and inform treatment decisions for patients at high risk of progression. Funding Science Foundation of Chinese Ministry of Health, National Natural Science Foundation of China, Pearl River Scholar Funded Scheme, Guangdong Key Scientific and Technological Innovation Program, Guangdong Natural Science Foundation, Fundamental Research Funds for the Central Universities.
Long non-coding RNAs (lncRNAs) have been identified as essential mediators in neurological dysfunction. Our previous study shows that berberine (BBR) hampers the nuclear-to-cytosolic translocation of ...high-mobility group box 1 (HMGB1) in the process of poststroke inflammation. In this study, we explored the role of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (Malat1) in the process of BBR-induced inhibition of HMGB1 in ischemic brain. Before the 60-min MCAO surgery, the mice were pretreated with BBR (50 mg· kg
per day, ig) for 14 days or ICV injected with specific lentiviral vector or shRNA. We showed that MCAO caused marked increase in the expression Malat1 and HMGB1 in the ipsilateral cortex, which was significantly attenuated by pretreatment with BBR. Knockdown of Malat1 attenuated the inflammatory injury after brain ischemia, whereas overexpression of Malat1 exacerbated ischemic brain inflammation. Overexpression of Malat1 also reversed BBR-induced reduction of HMGB1 and proinflammatory cytokines. The above results suggested a potential correlation between Malat1 and stroke inflammation. Based on informatics analysis we predicted that HMGB1 was a direct downstream target of miR-181c-5p, whereas Malat1 acted as a competitive endogenous RNA (ceRNA) for miR-181c-5p targeted the 3'-UTR of HMGB1 to promote inflammation after ischemic stroke. Knockdown of Malat1 significantly decreased HMGB1 level, which could be abrogated by transfection with miR-181c-5p inhibitors. Taken together, our results demonstrate for the first time that Malat1/miR-181c-5p/HMGB1 axis may be a key pathway of BBR-induced antiinflammation effects in stroke, and they may provide a novel avenue for targeted therapy.
Two-dimensional (2D) metal–organic framework nanosheets (MONs) or membranes are classes of periodic, crystalline polymeric materials that may show unprecedented physicochemical properties due to ...their modular structures, high surface areas, and high aspect ratios. Yet preparing 2D MONs from multiple components and two different types of polymerization reaction remains challenging and less explored. Here, we report the synthesis of MOF films via interfacial polymerization, which involves three active monomers for simultaneous polycondensation and polycoordination taking place in a confined interface. The well-defined lamellar structure of the MOF films allowed feasible and scalable exfoliation to produce free-standing 2D MONs with high aspect ratio up to 2000:1 and ultrathin thickness (∼1.7 nm). The pore structure was revealed by high-resolution TEM images with near-atomic precision. The imide-linkage of MONs provided superior thermal (up to 530 °C) and good chemical stability in the pH range from 3 to 12. More importantly, the MONs exhibited exceptional catalytic activity and superior reusability for the hydroboration reactions of alkynes, in which the turnover frequency (TOF) reached 41734 h–1, which is 2–4 orders of magnitude greater than that reported for homogeneous and heterogeneous catalysts.
Background
During endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA), cytopathology with rapid on‐site evaluation (ROSE) can improve diagnostic yield and accuracy. However, ROSE is ...unavailable in most Asian and European institutions because of the shortage of cytopathologists. Therefore, developing computer‐assisted diagnostic tools to replace manual ROSE is crucial. Herein, we reported the validation of an artificial intelligence (AI)‐based model (ROSE‐AI model) to substitute manual ROSE during EUS‐FNA.
Methods
A total of 467 digitized images from Diff‐Quik (D&F)‐stained EUS‐FNA slides were divided into training (3642 tiles from 367 images) and internal validation (916 tiles from 100 images) datasets. The ROSE‐AI model was trained and validated using training and internal validation datasets, respectively. The specificity was emphasized while developing the model. Then, we evaluated the AI model on a 693‐image external dataset. We assessed the performance of the AI model to detect cancer cells (CCs) regarding the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).
Results
The ROSE‐AI model achieved an accuracy of 83.4% in the internal validation dataset and 88.7% in the external test dataset. The sensitivity and PPV were 79.1% and 71.7% in internal validation dataset and 78.0% and 60.7% in external test dataset, respectively.
Conclusion
We provided a proof of concept that AI can be used to replace manual ROSE during EUS‐FNA. The ROSE‐AI model can address the shortage of cytopathologists and make ROSE available in more institutes.
Interest in piezochromic luminescence has increased in recent decades, even though it is mostly limited to pure organic compounds and fluorescence. In this work, a Cu
3
Pz
3
(
Cu
3
, Pz: pyrazolate) ...cyclic trinuclear complex (CTC) with two different crystalline polymorphs, namely
1a
and
1b
, was synthesized. The CTC consists of two functional moieties: carbazole (
Cz
) chromophore and
Cu
3
units. In crystals of
1a
, discrete
Cz
-
Cu
3
-
Cu
3
-
Cz
stacking was found, showing abnormal pressure-induced phosphorescence enhancement (PIPE), which was 12 times stronger at 2.23 GPa compared to under ambient conditions. This novel observation is ascribed to cooperation between heavy-atom effects (
i.e.
, from Cu atoms) and metal-ligand charge-transfer promotion. The infinite π-π stacking of
Cz
motifs was observed in
1b
and it exhibited good piezochromism as the pressure increased. This work demonstrates a new concept in the design of piezochromic materials to achieve PIPE
via
combining organic chromophores and metal-organic phosphorescence emitters.
One molecule, two response mechanisms: a pair of newly-designed cyclic trinuclear Cu(
i
) complex crystalline polymorphs are engineered, which show excellent luminescent piezochromism and pressure-induced phosphorescence enhancement, respectively.
The design of adsorbents for rapid, selective extraction of ultra-trace amounts of gold from complex liquids is desirable from both an environmental and economical point of view. However, the ...development of such materials remains challenging. Herein, we report the fabrication of two vinylene-linked two-dimensional silver(I)-organic frameworks prepared via Knoevenagel condensation. This material enables selective sensing of gold with a low limit of detection of 60 ppb, as well as selective uptake of ultra-trace gold from complex aqueous mixtures including distilled water with 15 competing metal ions, leaching solution of electronic waste (e-waste), wastewater, and seawater. The present adsorbent delivers a gold adsorption capacity of 954 mg g
, excellent selectivity and reusability, and can rapidly and selectively extract ultra-trace gold from seawater down to ~20 ppb (94% removal in 10 minutes). In addition, the purity of recovered gold from e-waste reaches 23.8 Karat (99.17% pure).
Coronavirus disease 2019 (COVID-19) has killed over 2.5 million people worldwide, but effective care and therapy have yet to be discovered. We conducted this analysis to better understand tocilizumab ...treatment for COVID-19 patients.
We searched major databases for manuscripts reporting the effects of tocilizumab on COVID-19 patients. A total of 25 publications were analyzed with Revman 5.3 and R for the meta-analysis. Significant better clinical outcomes were found in the tocilizumab treatment group when compared to the standard care group odds ratio (OR) = 0.70, 95% confidential interval (C): 0.54-0.90, P = 0.007. Tocilizumab treatment showed a stronger correlation with good prognosis among COVID-19 patients that needed mechanical ventilation (OR = 0.59, 95% CI, 0.37-0.93, P = 0.02). Among stratified analyses, reduction of overall mortality correlates with tocilizumab treatment in patients less than 65 years old (OR = 0.68, 95% CI: 0.60-0.77, P < 0.00001), and with intensive care unit patients (OR = 0.62, 95% CI: 0.55-0.70, P < 0.00001). Pooled estimates of hazard ratio showed that tocilizumab treatment predicts better overall survival in COVID-19 patients (HR = 0.45, 95% CI: 0.24-0.84, P = 0.01), especially in severe cases (HR = 0.58, 95% CI 0.49-0.68, P < 0.00001).
Our study shows that tocilizumab treatment is associated with a lower risk of mortality and mechanical ventilation requirement among COVID-19 patients. Tocilizumab may have substantial effectiveness in reducing mortality among COVID-19 patients, especially among critical cases. This systematic review provides an up-to-date evidence of potential therapeutic role of tocilizumab in COVID-19 management.
Inflammatory damage plays an important role in cerebral ischemic pathogenesis and represents a new target for treatment of stroke. Berberine is a natural medicine with multiple beneficial biological ...activities. In this study, we explored the mechanisms underlying the neuroprotective action of berberine in mice subjected transient middle cerebral artery occlusion (tMCAO). Male mice were administered berberine (25, 50 mg/kg/d, intragastric; i.g.), glycyrrhizin (50 mg/kg/d, intraperitoneal), or berberine (50 mg/kg/d, i.g.) plus glycyrrhizin (50 mg/kg/d, intraperitoneal) for 14 consecutive days before tMCAO. The neurological deficit scores were evaluated at 24 h after tMCAO, and then the mice were killed to obtain the brain samples. We showed that pretreatment with berberine dose-dependently decreased the infarct size, neurological deficits, hispathological changes, brain edema, and inflammatory mediators in serum and ischemic cortical tissue. We revealed that pretreatment with berberine significantly enhanced uptake of
F-fluorodeoxyglucose of ischemic hemisphere comparing with the vehicle group at 24 h after stroke. Furthermore, pretreatment with berberine dose-dependently suppressed the nuclear-to cytosolic translocation of high-mobility group box1 (HMGB1) protein, the cytosolic-to nuclear translocation of nuclear factor kappa B (NF-κB) and decreased the expression of TLR4 in ischemic cortical tissue. Moreover, co-administration of glycyrrhizin and berberine exerted more potent suppression on the HMGB1/TLR4/NF-κB pathway than berberine or glycyrrhizin administered alone. These results demonstrate that berberine protects the brain from ischemia-reperfusion injury and the mechanism may rely on its anti-inflammatory effects mediated by suppressing the activation of HMGB1/TLR4/NF-κB signaling.
Promoter engineering is an enabling technology in metabolic engineering and synthetic biology. As an indispensable part of synthetic biology, the promoter is a key factor in regulating genetic ...circuits and in coordinating multi-gene biosynthetic pathways. In this review, we summarized the recent progresses in promoter engineering in microbes. Specifically, the endogenous promoters are firstly discussed, followed by the statement of the influence of nucleotides exchange on the strength of promoters explored by site-selective mutagenesis. We then introduced the promoter libraries with a wide range of strength, which are constructed focusing on core promoter regions and upstream activating sequences by rational designs. Finally, the application of promoter libraries in the optimization of multi-gene metabolic pathways for high-yield production of metabolites was illustrated with a couple of recent examples.
The rebound of influenza A (H1N1) infection in post-COVID-19 era recently attracted enormous attention due the rapidly increased number of pediatric hospitalizations and the changed characteristics ...compared to classical H1N1 infection in pre-COVID-19 era. This study aimed to evaluate the clinical characteristics and severity of children hospitalized with H1N1 infection during post-COVID-19 period, and to construct a novel prediction model for severe H1N1 infection.
A total of 757 pediatric H1N1 inpatients from nine tertiary public hospitals in Yunnan and Shanghai, China, were retrospectively included, of which 431 patients diagnosed between February 2023 and July 2023 were divided into post-COVID-19 group, while the remaining 326 patients diagnosed between November 2018 and April 2019 were divided into pre-COVID-19 group. A 1:1 propensity-score matching (PSM) was adopted to balance demographic differences between pre- and post-COVID-19 groups, and then compared the severity across these two groups based on clinical and laboratory indicators. Additionally, a subgroup analysis in the original post-COVID-19 group (without PSM) was performed to investigate the independent risk factors for severe H1N1 infection in post-COIVD-19 era. Specifically, Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to select candidate predictors, and logistic regression was used to further identify independent risk factors, thus establishing a prediction model. Receiver operating characteristic (ROC) curve and calibration curve were utilized to assess discriminative capability and accuracy of the model, while decision curve analysis (DCA) was used to determine the clinical usefulness of the model.
After PSM, the post-COVID-19 group showed longer fever duration, higher fever peak, more frequent cough and seizures, as well as higher levels of C-reactive protein (CRP), interleukin 6 (IL-6), IL-10, creatine kinase-MB (CK-MB) and fibrinogen, higher mechanical ventilation rate, longer length of hospital stay (LOS), as well as higher proportion of severe H1N1 infection (all P < 0.05), compared to the pre-COVID-19 group. Moreover, age, BMI, fever duration, leucocyte count, lymphocyte proportion, proportion of CD3
T cells, tumor necrosis factor α (TNF-α), and IL-10 were confirmed to be independently associated with severe H1N1 infection in post-COVID-19 era. A prediction model integrating these above eight variables was established, and this model had good discrimination, accuracy, and clinical practicability.
Pediatric H1N1 infection during post-COVID-19 era showed a higher overall disease severity than the classical H1N1 infection in pre-COVID-19 period. Meanwhile, cough and seizures were more prominent in children with H1N1 infection during post-COVID-19 era. Clinicians should be aware of these changes in such patients in clinical work. Furthermore, a simple and practical prediction model was constructed and internally validated here, which showed a good performance for predicting severe H1N1 infection in post-COVID-19 era.
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