ß-Elemene Reverses Gefitinib Resistance in NSCLC Cells by Inhibiting lncRNA H19-Mediated Autophagy.

Lung cancer is a leading cause of mortality worldwide, especially among Asian patients with non-small cell lung cancer (NSCLC) who have epidermal growth factor receptor (EGFR) mutations. Initially, first-generation EGFR tyrosine kinase inhibitors (TKIs) are commonly administered as the primary treatment option; however, encountering resistance to these medications poses a significant obstacle. Hence, it has become crucial to address initial resistance and ensure continued effectiveness. Recent research has focused on the role of long noncoding RNAs (lncRNAs) in tumor drug resistance, especially lncRNA H19. ß-elemene, derived from Curcuma aromatic Salisb., has shown strong anti-tumor effects. However, the relationship between ß-elemene, lncRNA H19, and gefitinib resistance in NSCLC is unclear. This study aims to investigate whether ß-elemene can enhance the sensitivity of gefitinib-resistant NSCLC cells to gefitinib and to elucidate its mechanism of action. The impact of gefitinib and ß-elemene on cell viability was evaluated using the cell counting kit-8 (CCK8) assay. Furthermore, western blotting and qRT-PCR analysis were employed to determine the expression levels of autophagy-related proteins and genes, respectively. The influence on cellular proliferation was gauged through a colony-formation assay, and apoptosis induction was quantified via flow cytometry. Additionally, the tumorigenic potential in vivo was assessed using a xenograft model in nude mice. The expression levels of LC3B, EGFR, and Rab7 proteins were examined through immunofluorescence. Our findings elucidate that the resistance to gefitinib is intricately linked with the dysregulation of autophagy and the overexpression of lncRNA H19. The synergistic administration of ß-elemene and gefitinib markedly attenuated the proliferative capacity of resistant cells, expedited apoptotic processes, and inhibited the in vivo proliferation of lung cancer. Notably, ß-elemene profoundly diminished the expression of lncRNA H19 and curtailed autophagic activity in resistant cells, thereby bolstering their responsiveness to gefitinib. Moreover, ß-elemene disrupted the Rab7-facilitated degradation pathway of EGFR, facilitating its repositioning to the plasma membrane. ß-elemene emerges as a promising auxiliary therapeutic for circumventing gefitinib resistance in NSCLC, potentially through the regulation of lncRNA H19-mediated autophagy. The participation of Rab7 in this dynamic unveils novel insights into the resistance mechanisms operative in lung cancer, paving the way for future therapeutic innovations.

Recent Advances in Photosensitizer Materials for Light-Mediated Tumor Therapy.

Photodynamic therapy (PDT) as an emerging therapeutic method has drawn much attention in the treatment field for cancer. Photosensitizer, which can convert photon energy into cytotoxic species under light irradiation, is the core component in PDT. The design of photosensitizers still faces problems of light absorption, targeting, penetration and oxygen dependence. With the rapid progress of material science, various photosensitizers have been developed to produce cytotoxic species for treatment of tumor with high selectivity, safety, and noninvasiveness. Besides, the applications of photosensitizers have been expanded to diverse cancer treatments such as drug release, optogenetics and immune checkpoint blockade. In this review, we summarize the recent advances of photosensitizers in various therapeutic methods for cancer. Prevailing challenges and further prospects associated with photosensitizers are also discussed.

A Recombinant Thermophilic and Glucose-Tolerant GH1 ß-Glucosidase Derived from Hehua Hot Spring.

As a crucial enzyme for cellulose degradation, ß-glucosidase finds extensive applications in food, feed, and bioethanol production; however, its potential is often limited by inadequate thermal stability and glucose tolerance. In this study, a functional gene (lq-bg5) for a GH1 family ß-glucosidase was obtained from the metagenomic DNA of a hot spring sediment sample and heterologously expressed in E. coli and the recombinant enzyme was purified and characterized. The optimal temperature and pH of LQ-BG5 were 55 °C and 4.6, respectively. The relative residual activity of LQ-BG5 exceeded 90% at 55 °C for 9 h and 60 °C for 6 h and remained above 100% after incubation at pH 5.0-10.0 for 12 h. More importantly, LQ-BG5 demonstrated exceptional glucose tolerance with more than 40% activity remaining even at high glucose concentrations of 3000 mM. Thus, LQ-BG5 represents a thermophilic ß-glucosidase exhibiting excellent thermal stability and remarkable glucose tolerance, making it highly promising for lignocellulose development and utilization.

Longitudinal proteomic investigation of COVID-19 vaccination.

Although the development of COVID-19 vaccines has been a remarkable success, the heterogeneous individual antibody generation and decline over time are unknown and still hard to predict. In this study, blood samples were collected from 163 participants who next received two doses of an inactivated COVID-19 vaccine (CoronaVac®) at a 28-day interval. Using TMT-based proteomics, we identified 1,715 serum and 7,342 peripheral blood mononuclear cells (PBMCs) proteins. We proposed two sets of potential biomarkers (seven from serum, five from PBMCs) at baseline using machine learning, and predicted the individual seropositivity 57 days after vaccination (AUC = 0.87). Based on the four PBMC's potential biomarkers, we predicted the antibody persistence until 180 days after vaccination (AUC = 0.79). Our data highlighted characteristic hematological host responses, including altered lymphocyte migration regulation, neutrophil degranulation, and humoral immune response. This study proposed potential blood-derived protein biomarkers before vaccination for predicting heterogeneous antibody generation and decline after COVID-19 vaccination, shedding light on immunization mechanisms and individual booster shot planning.

Aberrant Spontaneous Brain Activity and its Association with Cognitive Function in Non-Obese Nonalcoholic Fatty Liver Disease: A Resting-State fMRI Study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has been proven to be associated with an increased risk of cognitive impairment and dementia, and this association is more significant in non-obese NAFLD populations, but its pathogenesis remains unclear. Our study aimed to explore the abnormalities of spontaneous brain activity in non-obese NAFLD patients by resting-state fMRI (RS-fMRI) and their relationship with cognitive function. METHODS: 19 non-obese NAFLD, 25 obese NAFLD patients, and 20 healthy controls (HC) were enrolled. All subjects underwent RS-fMRI scan, psychological scale assessment, and biochemical examination. After RS-fMRI data were preprocessed, differences in low-frequency fluctuation amplitude (ALFF), regional homogeneity (ReHo) and functional connectivity (FC) were compared among the three groups. Furthermore, the relationship between RS-fMRI indicators and cognitive and clinical indicators were performed using correlation analysis. RESULTS: The cognitive function was declined in both NAFLD groups. Compared with obese NAFLD patients, non-obese NAFLD patients showed increased ALFF and ReHo in the left middle temporal gyrus (MTG), increased ReHo in the sensorimotor cortex and reduced FC between left MTG and right inferior frontal gyrus (IFG). Compared with HC, non-obese NAFLD patients showed increased ALFF and ReHo in the left calcarine cortex and fusiform gyrus (FG), decreased ALFF in the bilateral cerebellum, and reduced FC between left FG and right IFG and left angular gyrus. In addition to the same results, obese patients showed increased activity in different regions of the bilateral cerebellum, while decreased ALFF in the right superior frontal gyrus and ReHo in the right orbitofrontal cortex (OFC). Correlation analysis showed that in non-obese patients, the ALFF values in the FG and the FC values between the left MTG and the right IFG were associated with cognitive decline, insulin resistance, and fasting glucose disorder. CONCLUSIONS: Non-obese NAFLD patients showed abnormal local spontaneous activity and FC in regions involved in the sensorimotor, temporo-occipital cortex, cerebellum, and reward system (such as OFC), some of which may be the potential neural mechanism difference from obese NAFLD patients. In addition, the temporo-occipital cortex may be a vulnerable target for cognitive decline in non-obese NAFLD patients.

Serum metabolomics-based heterogeneities and screening strategy for metabolic dysfunction-associated fatty liver disease (MAFLD).

BACKGROUND AND AIMS: Metabolic dysfunction-associated fatty liver disease (MAFLD) brings heavy clinical and economic burdens to society, while understandings on heterogeneities are limited. MATERIALS AND METHODS: We conducted a serum metabolomics study to reveal the metabolic heterogeneities and develop a diagnostic strategy for MAFLD using a discovery set consisting of 122 biopsy-proven MAFLD patients [lean (n = 12), overweight (n = 20), obese (n = 74), type 2 diabetes mellitus (T2DM, n = 16)] and 35 controls, and a validation set containing 60 biopsy-proven MAFLD patients (20 lean, 20 obese and 20 T2DM) and 20 controls. RESULTS: Mitochondrial dysfunction, destructed phospholipids homeostasis, and folate deficiency were most severe in MAFLD concurrent T2DM patients. Formiminoglutamate, sphinganine and sphingosine correlated positively with HbA1c, while glycoursodeoxycholicacidsulfate correlated positively with AST. Additionally, the linear discriminant analysis (LDA) model using metabolites 5-hydroxyhexanoate, ribitol and formiminoglutamate demonstrated pretty good performance in screening for MAFLD patients, with AUC for validation samples being 0.94 (CI: 0.88-1.0). For easier clinical applications, an M-index based on the three metabolites was further designed. CONCLUSION: Our study supports that MAFLD concurrent T2DM patients deserve particular attentions in clinical follow-up, and paves the way for developing more effective diagnostic options in future studies.

Blood pressure stratification for predicting liver fibrosis risk in metabolic dysfunction associated fatty liver disease.

INTRODUCTION AND OBJECTIVES: The optimal blood pressure (BP) range for patients with metabolic dysfunction-associated fatty liver disease (MAFLD) is currently unknown. This study aimed to explore the relationship between stratified BP levels and MAFLD progression. PATIENTS AND METHODS: The data of adults who underwent yearly health check-ups were screened to establish both a cross-sectional and a 6-year longitudinal cohort of individuals with MAFLD. BP was classified into the following categories optimal, normal, high-normal, and hypertension. Liver fibrosis was diagnosed with fibrosis-4 (FIB-4) score, nonalcoholic fatty liver disease fibrosis score (NFS), and aspartate aminotransferase-to-platelet ratio index (APRI). RESULTS: A total of 10,232 individuals were included in the cross-sectional cohort. In the MAFLD population, individuals with liver fibrosis had significantly higher BP levels and hypertension prevalence (P < 0.001) than those without. Furthermore, liver fibrosis score was significantly associated with BP levels (P < 0.001). In the 6-year longitudinal cohort of 3661 individuals with MAFLD without liver fibrosis, the incidence rates of liver fibrosis increased with increasing BP levels as follows optimal=11.20%, normal=13.90%, high-normal=19.50%, hypertension=26.20% (log-rank 22.205; P < 0.001). Cox regression analysis showed that both baseline high-normal BP (hazard ratio [HR], 1.820; P=0.019) and hypertension (HR, 2.656; P < 0.001) were predictive of liver fibrosis. CONCLUSIONS: BP stratification may be useful in predicting the progression of MAFLD. Individuals having MAFLD with concurrent hypertension or high-normal BP are at a higher risk of liver fibrosis. These findings may provide a criteria for early intervention of MAFLD to prevent liver fibrosis.

Identification of genes modified by N6-methyladenosine in patients with colorectal cancer recurrence.

Background: Recent studies demonstrate that N6-methyladenosine (m6A) methylation plays a crucial role in colorectal cancer (CRC). Therefore, we conducted a comprehensive analysis to assess the m6A modification patterns and identify m6A-modified genes in patients with CRC recurrence. Methods: The m6A modification patterns were comprehensively evaluated by the NMF algorithm based on the levels of 27 m6A regulators, and tumor microenvironment (TME) cell-infiltrating characteristics of these modification patterns were systematically assessed by ssGSEA and CIBERSORT algorithms. The principal component analysis algorithm based on the m6A scoring scheme was used to explore the m6A modification patterns of individual tumors with immune responses. The weighted correlation network analysis and univariable and multivariable Cox regression analyses were applied to identify m6A-modified gene signatures. The single-cell expression dataset of CRC samples was used to explore the tumor microenvironment affected by these signatures. Results: Three distinct m6A modification patterns with significant recurrence-free survival (RFS) were identified in 804 CRC patients. The TME characterization revealed that the m6A modification pattern with longer RFS exhibited robust immune responses. CRC patients were divided into high- and low-score subgroups according to the m6A score individually, which was obtained from the m6A-related signature genes. The patients with low m6A scores had both longer RFS and overall survival (OS) with altered immune cell infiltration. Notably, m6A-modified genes showed significant differences related to the prognosis of CRC patients in the meta-GEO cohort and TCGA cohort. Single-cell expression indicated that ALVRL1 was centrally distributed in endothelial tip cells and stromal cells. Conclusion: The m6A modification plays an indispensable role in the formation of TME diversity and complexity. Importantly, the signatures (TOP2A, LRRC58, HAUS6, SMC4, ACVRL1, and KPNB1) were identified as m6A-modified genes associated with CRC recurrence, thereby serving as a promising predictive biomarker or therapeutic target for patients with CRC recurrence.

Anoikis-Associated Lung Cancer Metastasis: Mechanisms and Therapies.

Tumor metastasis occurs in lung cancer, resulting in tumor progression and therapy failure. Anoikis is a mechanism of apoptosis that combats tumor metastasis; it inhibits the escape of tumor cells from the native extracellular matrix to other organs. Deciphering the regulators and mechanisms of anoikis in cancer metastasis is urgently needed to treat lung cancer. Several natural and synthetic products exhibit the pro-anoikis potential in lung cancer cells and in vivo models. These products include artonin E, imperatorin, oroxylin A, lupalbigenin, sulforaphane, renieramycin M, avicequinone B, and carbenoxolone. This review summarizes the current understanding of the molecular mechanisms of anoikis regulation and relevant regulators involved in lung cancer metastasis and discusses the therapeutic potential of targeting anoikis in the treatment of lung cancer metastasis.

The Pharmacological Mechanism of Curcumin against Drug Resistance in Non-Small Cell Lung Cancer: Findings of Network Pharmacology and Bioinformatics Analysis.

The pharmacological mechanism of curcumin against drug resistance in non-small cell lung cancer (NSCLC) remains unclear. This study aims to summarize the genes and pathways associated with curcumin action as an adjuvant therapy in NSCLC using network pharmacology, drug-likeness, pharmacokinetics, functional enrichment, protein-protein interaction (PPI) analysis, and molecular docking. Prognostic genes were identified from the curcumin-NSCLC intersection gene set for the following drug sensitivity analysis. Immunotherapy, chemotherapy, and targeted therapy sensitivity analyses were performed using external cohorts (GSE126044 and IMvigor210) and the CellMiner database. 94 curcumin-lung adenocarcinoma (LUAD) hub targets and 41 curcumin-lung squamous cell carcinoma (LUSC) hub targets were identified as prognostic genes. The anticancer effect of curcumin was observed in KEGG pathways involved with lung cancer, cancer therapy, and other cancers. Among the prognostic curcumin-NSCLC intersection genes, 20 LUAD and 8 LUSC genes were correlated with immunotherapy sensitivity in the GSE126044 NSCLC cohort; 30 LUAD and 13 LUSC genes were associated with immunotherapy sensitivity in the IMvigor210 cohort; and 12 LUAD and 13 LUSC genes were related to chemosensitivity in the CellMiner database. Moreover, 3 LUAD and 5 LUSC genes were involved in the response to targeted therapy in the CellMiner database. Curcumin regulates drug sensitivity in NSCLC by interacting with cell cycle, NF-kappa B, MAPK, Th17 cell differentiation signaling pathways, etc. Curcumin in combination with immunotherapy, chemotherapy, or targeted drugs has the potential to be effective for drug-resistant NSCLC. The findings of our study reveal the relevant key signaling pathways and targets of curcumin as an adjuvant therapy in the treatment of NSCLC, thus providing pharmacological evidence for further experimental research.

The Synergism of Natural Compounds and Conventional Therapeutics against Colorectal Cancer Progression and Metastasis.

Cancer progression and metastases are the leading causes of poor outcomes in patients with colon cancer. Colon cancer metastasis is a multigene, multistep, multistage complex process in which target genes, microRNAs, epithelial-stromal transformation, tumour stem cells, the tumour microenvironment, and various cell signalling pathways are implicated in the progression and metastasis of colon cancer. Although conventional therapies have made significant advances in treating the progression and metastasis of colorectal cancer, they have failed to improve survival outcomes. Natural compounds may have more significant potential in preventing and treating colon cancer. Active natural compounds exert their antitumor effects by inducing tumour cell differentiation, promoting tumour cell apoptosis, inhibiting tumour vascular growth, and regulating immunity. Natural compounds, combined with conventional therapies, can target mutant genes and various cellular signalling pathways, inhibit epithelial-stromal transformation, and improve the tumour microenvironment to inhibit tumour progression and metastasis. The synergism of natural compounds and conventional therapeutics has the potential to become a promising therapy for treating colorectal cancer progression and metastases.

The Role and Therapeutic Potential of Macropinocytosis in Cancer.

Macropinocytosis, a unique endocytosis pathway characterized by nonspecific internalization, has a vital role in the uptake of extracellular substances and antigen presentation. It is known to have dual effects on cancer cells, depending on cancer type and certain microenvironmental conditions. It helps cancer cells survive in nutrient-deficient environments, enhances resistance to anticancer drugs, and promotes invasion and metastasis. Conversely, overexpression of the RAS gene alongside drug treatment can lead to methuosis, a novel mode of cell death. The survival and proliferation of cancer cells is closely related to macropinocytosis in the tumor microenvironment (TME), but identifying how these cells interface with the TME is crucial for creating drugs that can limit cancer progression and metastasis. Substantial progress has been made in recent years on designing anticancer therapies that utilize the effects of macropinocytosis. Both the induction and inhibition of macropinocytosis are useful strategies for combating cancer cells. This article systematically reviews the general mechanisms of macropinocytosis, its specific functions in tumor cells, its occurrence in nontumor cells in the TME, and its application in tumor therapies. The aim is to elucidate the role and therapeutic potential of macropinocytosis in cancer treatment.

Identification of Genes Related to 5-Fluorouracil Based Chemotherapy for Colorectal Cancer.

Background: Colorectal cancer (CRC) is one of the most common malignancies and its incidence and mortality are increasing yearly. 5-Fluorouracil (5-FU) has long been used as a standard first-line treatment for CRC patients. Although 5-FU-based chemotherapy is effective for advanced CRC, the consequent resistance remains a key problem and causes the poor prognosis of CRC patients. Thus, there is an urgent need to identify new biomarkers to predict the response to 5-FU-based chemotherapy. Methods: CRC samples were retrieved from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). The immune-related genes were retrieved from the ImmPort database. Single-cell sequencing results from colorectal cancer were obtained by the ArrayExpress database. 5-FU resistance-related genes were filtered and validated by R packages. ESTIMATE algorithms were used to assess the tumor microenvironment (TME). KEGG and GO analysis were performed to explore the biological signaling pathway for resistant-response patients and sensitive-response patients in the tumor microenvironment. pRRophetic algorithms were used to predict 5-FU sensitivity. GSEA and GSVA analysis was performed to excavate the biological signaling pathway of the RBP7 gene. Results: Nine immune-related genes were identified to be associated with 5-FU resistance and poor disease-free survival (DFS) of CRC patients and the signature of these genes was developed in a DFS-prognostic model. Four immune-related genes were determined to be associated with 5-FU resistance and overall survival (OS) of CRC patients. The signature of these genes was developed an OS-prognostic model. ESTIMATE scores showed a significant difference between 5-FU resistant and 5-FU sensitive CRC patients. Resistant-response patients and sensitive-response patients to 5-FU based chemotherapy showed different GO and KEGG enrichment on the tumor microenvironment. RBP7, as a tumor immune microenvironment (TIME) related gene, was found to have the potential of predicting chemotherapy resistance and poor prognosis of CRC patients. GSEA analysis showed multiple signaling differences between the high and low expression of RBP7 in CRC patients. Hypoxia and TNFα signaling via NFκB gene sets were significantly different between chemotherapy resistant (RBP7High) and chemotherapy sensitive (RBP7Low) patients. Single-cell RNA-seq suggested RBP7 was centrally distributed in endothelial stalk cells, endothelial tip cells, and myeloid cells. Conclusions: Immune-related genes will hopefully be potential prognostic biomarkers to predict chemotherapy resistance for CRC. RBP7 may function as a tumor microenvironment regulator to induce 5-FU resistance, thereby affecting the prognosis of CRC patients.

A Novel Diagnostic and Therapeutic Strategy for Cancer Patients by Integrating Chinese Medicine Syndrome Differentiation and Precision Medicine.

Applying Chinese medicine (CM) is an important strategy for malignant tumor treatment in China. One of the significant characteristics of CM is to treat diseases based on syndrome differentiation. For Western medicine, it is of important clinical significance to formulate guidelines for the diagnosis and treatment of cancer patients based on the characteristics of disease differentiation. In Chinese clinical practice, the combination of disease differentiation and syndrome differentiation is an important feature for cancer treatment in the past. Currently, molecular profiling and genomic analysis-based precision medicine optimizes the anticancer drug design and holds the greatest success in treating cancer patients. Therefore, we want to know which populations of cancer patients can benefit more from CM treatment if the theory of precision medicine is applied to CM clinical practice. So, we developed a novel diagnostic and therapeutic strategy "disease-syndrome differentiation-genomic profiling-prescriptions" for cancer patients by CM syndrome differentiation and precision medicine. As a result, this strategy has greatly enhanced the anti-tumor efficacy of CM and improved clinical outcomes for cancer patients with some gene mutations. Our idea will hopefully establish a novel approach for the inheritance and innovation of CM.

Curcumenol triggered ferroptosis in lung cancer cells via lncRNA H19/miR-19b-3p/FTH1 axis.

Curcumenol, an effective ingredient of Wenyujin, has been reported that exerted its antitumor potential in a few cancer types. However, the effect and molecular mechanism of curcumenol in lung cancer are largely unknown. Here, we found that curcumenol induced cell death and suppressed cell proliferation in lung cancer cells. Next, we demonstrated that ferroptosis was the predominant method that contributed to curcumenol-induced cell death of lung cancer in vitro and vivo for the first time. Subsequently, using RNA sequencing, we found that the long non-coding RNA H19 (lncRNA H19) was significantly downregulated in lung cancer cells treated with curcumenol, when compared to untreated controls. Overexpression of lncRNA H19 eliminated the anticancer effect of curcumenol, while lncRNA H19 knockdown promoted ferroptosis induced by curcumenol treatment. Mechanistically, we showed that lncRNA H19 functioned as a competing endogenous RNA to bind to miR-19b-3p, thereby enhanced the transcription activity of its endogenous target, ferritin heavy chain 1 (FTH1), a marker of ferroptosis. In conclusion, our data show that the natural product curcumenol exerted its antitumor effects on lung cancer by triggering ferroptosis, and the lncRNA H19/miR-19b-3p/FTH1 axis plays an essential role in curcumenol-induced ferroptotic cell death. Therefore, our findings will hopefully provide a valuable drug for treating lung cancer patients.

A Markov Decision Process Approach for Cost-Benefit Analysis of Infrastructure Resilience Upgrades.

As climate change threatens to cause increasingly frequent and severe natural disasters, decisionmakers must consider costly investments to enhance the resilience of critical infrastructures. Evaluating these potential resilience improvements using traditional cost-benefit analysis (CBA) approaches is often problematic because disasters are stochastic and can destroy even hardened infrastructure, meaning that the lifetimes of investments are themselves uncertain. In this article, we develop a novel Markov decision process (MDP) model for CBA of infrastructure resilience upgrades that offer prevention (reduce the probability of a disaster) and/or protection (mitigate the cost of a disaster) benefits. Stochastic features of the model include disaster occurrences and whether or not a disaster terminates the effective life of an earlier resilience upgrade. From our MDP model, we derive analytical expressions for the decisionmaker's willingness to pay (WTP) to enhance infrastructure resilience, and conduct a comparative static analysis to investigate how the WTP varies with the fundamental parameters of the problem. Following this theoretical portion of the article, we demonstrate the applicability of our MDP framework to real-world decision making by applying it to two case studies of electric utility infrastructure hardening. The first case study considers elevating a flood-prone substation and the second assesses upgrading transmission structures to withstand high winds. Results from these two case studies show that assumptions about the value of lost load during power outages and the distribution of customer types significantly influence the WTP for the resilience upgrades and are material to the decisions of whether or not to implement them.

Ultrafast imaging of spontaneous symmetry breaking in a photoionized molecular system.

The Jahn-Teller effect is an essential mechanism of spontaneous symmetry breaking in molecular and solid state systems, and has far-reaching consequences in many fields. Up to now, to directly image the onset of Jahn-Teller symmetry breaking remains unreached. Here we employ ultrafast ion-coincidence Coulomb explosion imaging with sub-10 fs resolution and unambiguously image the ultrafast dynamics of Jahn-Teller deformations of [Formula: see text] cation in symmetry space. It is unraveled that the Jahn-Teller deformation from C3v to C2v geometries takes a characteristic time of 20 ± 7 fs for this system. Classical and quantum molecular dynamics simulations agree well with the measurement, and reveal dynamics for the build-up of the C2v structure involving complex revival process of multiple vibrational pathways of the [Formula: see text] cation.

Paper-based upconversion fluorescence aptasensor for the quantitative detection of immunoglobulin E in human serum.

Immunoglobulin E (IgE), a biomarker of allergic diseases, plays a critical role in allergic mechanism. Because of its low abundance in serum, the demand of developing sensitive, selective and simple methods for IgE detection is still very urgent. Paper-based analytical devices using upconversion nanoparticles (UCNPs) as the label can be promising point-of-care test (POCT) methods in rapid diagnosis, owing to their NIR-excitation and visible light emission nature, which can avoid the interference of autofluorescence and scattering light from biological samples and paper substrates. In this work, we proposed a paper-based analytical device for the sensitive, selective and accurate detection of total immunoglobulin E (IgE) in human serum. The assay was based on resonance energy transfer between UCNPs and organic dye tetramethylrhodamine (TAMRA), and IgE aptamer with stem-loop structure was used as the recognizing probe. The existence of IgE change the conformation of IgE aptamer, enlarge the distance between donor and acceptor, and block the energy transfer process. Thus, the luminescence of UCNPs recovered with an IgE concentration independent manner. A linear calibration was obtained in the range of 0.5-50 IU/mL, with a detection limit of 0.13 IU/mL. The results of our method were well correlated with that of commercial ELISA kit (20 human serum samples). This work suggests promising prospect of the paper-based UC-LRET analytical devices in real samples and may promote the application of paper-based analytical devices in clinical diagnosis.

Efficacy and safety of Xiyanping for COVID-2019: A protocol for systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global pandemic caused by the severe acute respiratory syndrome coronavirus-2.COVID-19 is highly pathogenic and infectious. COVID-19 epidemic is still spreading all over the world, and there is no sign of stopping at present. There is no specific cure for this disease, and the clinical management mainly depends on supportive treatment. Xiyanping is widely used in treating COVID-19 in China. However, there is no evidence that Xiyanping is effective and safe for COVID-19. METHODS: A comprehensive literature search will be conducted. Two methodological trained researchers will read the title, abstract, and full texts and independently select the qualified literature according to inclusion and exclusion criteria. After assessment of the risk of bias and data extraction, we will conduct meta-analysis for outcomes related to COVID-19. The heterogeneity of data will be investigated by Cochrane X and I tests. Then publication bias assessment will be conducted by funnel plot analysis and Egger test. RESULTS: The results of our research will be published in a peer-reviewed journal. CONCLUSION: Our study aims to systematically present the clinical evidence of Xiyanping in the treatment of COVID-19, which will be of guiding significance for further research and clinical practice. OPEN SCIENCE FRAMEWORK REGISTRATION NUMBER: 10.17605/OFS.IO/SW75F.