Dihydroartemisinin induces ferroptosis in T cell acute lymphoblastic leukemia cells by downregulating SLC7A11 and activating the ATF4­CHOP signaling pathway.

The present study aimed to investigate the anti-leukemic effects of dihydroartemisinin (DHA) on T-cell acute lymphoblastic leukemia (T-ALL) cell lines, Jurkat and Molt-4, and the underlying mechanisms. Cell Counting Kit-8 was performed to measure cell viability. Cell apoptosis and cell cycle distribution were assessed by flow cytometry. The expression levels of ATF4 and CHOP mRNA were assessed by reverse transcription-quantitative PCR, while the protein abundance of SLC7A11, GPX4, ATF4 and CHOP was determined by western blotting. Moreover, malondialdehyde, glutathione (GSH) and reactive oxygen species (ROS) assays were used to detect the levels of ferroptosis. The results showed that DHA suppressed T-ALL cell viability in vitro, and induced cell cycle arrest at S or G2/M phase. DHA also induced ROS burst, activated endoplasmic reticulum (ER) stress, disrupted the system Xc--GSH-GSH peroxidase 4 antioxidant system, and increased lipid peroxide accumulation, resulting in cell death. By contrast, the pharmacological inhibition of ferroptosis alleviated DHA-induced cell death, confirming that DHA induces T-ALL cell death via ferroptosis. Mechanistically, the effect of DHA on ferroptosis was partly mediated by downregulating SLC7A11 and upregulating the ATF4-CHOP signaling pathway, which is associated with ER stress. These results indicated that DHA may induce ferroptosis in T-ALL cell lines and could represent a promising therapeutic agent for treating T-ALL.

A randomized, double-blind, placebo-controlled phase I clinical trial of rotavirus inactivated vaccine (Vero cell) in a healthy adult population aged 18-49 years to assess safety and preliminary observation of immunogenicity.

We conducted a phase I, randomized, double-blind, placebo-controlled trial including healthy adults in Sui County, Henan Province, China. Ninety-six adults were randomly assigned to one of three groups (high-dose, medium-dose, and low-dose) at a 3:1 ratio to receive one vaccine dose or placebo. Adverse events up to 28 days after each dose and serious adverse events up to 6 months after all doses were reported. Geometric mean titers and seroconversion rates were measured for anti-rotavirus neutralizing antibodies using microneutralization tests. The rates of total adverse events in the placebo group, low-dose group, medium-dose group, and high-dose group were 29.17 % (12.62 %-51.09 %), 12.50 % (2.66 %-32.36 %), 50.00 % (29.12 %-70.88 %), and 41.67 % (22.11 %-63.36 %), respectively, with no significant difference in the experimental groups compared with the placebo group. The results of the neutralizing antibody assay showed that in the adult group, the neutralizing antibody geometric mean titer at 28 days after full immunization in the low-dose group was 583.01 (95 % confidence interval [CI]: 447.12-760.20), that in the medium-dose group was 899.34 (95 % CI: 601.73-1344.14), and that in the high-dose group was 1055.24 (95 % CI: 876.28-1270.75). The GMT of serum-specific IgG at 28 days after full immunization in the low-dose group was 3444.26 (95 % CI: 2292.35-5175.02), that in the medium-dose group was 6888.55 (95 % CI: 4426.67-10719.6), and that in the high-dose group was 7511.99 (95 % CI: 3988.27-14149.0). The GMT of serum-specific IgA at 28 days after full immunization in the low-dose group was 2332.14 (95 % CI: 1538.82-3534.45), that in the medium-dose group was 4800.98 (95 % CI: 2986.64-7717.50), and that in the high-dose group was 3204.30 (95 % CI: 2175.66-4719.27). In terms of safety, adverse events were mainly Grades 1 and 2, indicating that the safety of the vaccine is within the acceptable range in the healthy adult population. Considering the GMT and positive transfer rate of neutralizing antibodies for the main immunogenicity endpoints in the experimental groups, it was initially observed that the high-dose group had higher levels of neutralizing antibodies than the medium- and low-dose groups in adults aged 18-49 years. This novel inactivated rotavirus vaccine was generally well-tolerated in adults, and the vaccine was immunogenic in adults (ClinicalTrials.gov number, NCT04626856).

An ALP-responsive, anionic iridium complex for specific recognition of osteosarcoma cells.

Poor cellular permeability greatly hampers the utilization of anionic Ir(III) complexes, though efficiently emissive and remarkably stable, in cell-based diagnosis. To overcome this barrier, we present the development of an alkaline phosphatase (ALP)-responsive, anionic, and aggregation-induced emission (AIE)-active Ir(III) complex (Ir1) for specific recognition of osteosarcoma cells. Containing phosphate moieties, Ir1 exhibits a net -1 charge, enabling charge repulsion from the cell membrane and resulting in low cellular uptake and good biocompatibility in normal osteoblast cells. Upon ALP-mediated hydrolysis of phosphate groups, the resulting dephosphorylated product, Ir2, demonstrates a positive charge and increased lipophilicity, promoting cellular uptake and activating its AIE properties for specific recognition of osteosarcoma cells that express elevated levels of ALP. This study elucidates the role of ALP as an ideal trigger for enhancing the cellular permeability of phosphate ester-containing Ir(III) complexes, thus expanding the potential of anionic Ir(III) complexes for biomedical applications.

Clinical presentation of severe COVID­19 with heart failure: A single­center retrospective study.

The coronavirus disease-19 (COVID-19) pandemic has led to a global transformation in public health interventions. The present study aimed to evaluate the clinical features as well as the outcomes of severe heart failure (HF) among patients with severe COVID-19. A single-center observational study was carried out at The 904th Hospital of Joint Logistic Support Force (Wuxi, China) from November 2022 to April 2023, and a total of 210 patients diagnosed with severe HF were included. Among these patients, 128 patients had COVID-19 whereas the remaining patients were not diagnosed with COVID-19. The analysis entailed investigated pre-existing medical records, that is, admission and discharge, laboratory values, neuroimaging, length of hospitalization, mortality and costs incurred by patients throughout the COVID-19 pandemic from the records. All the 210 incorporated patients accomplished the follow-up and it was established that there was no significant differences in baseline characteristics between HF combined with COVID-19 and HF without COVID-19 were affirmed (P>0.05). HF coupled with COVID-19 infection demonstrated an increased risk of 30-day mortality (28.91 vs. 14.63%; P=0.017), extended length of hospital stays (22.54±6.73 vs. 19.35±5.69; P<0.001) and higher expenses for hospitalization (P<0.001). Complications related to hospitalization, including pneumonia (76.56 vs. 35.37%; P=1.0x10-4), respiratory failure (47.66 vs. 24.39%; P=0.001), pulmonary embolism (8.59 vs. 2.44%; P=0.031), deep vein thrombosis (30.47 vs. 14.63%; P=0.009), 7 days delirium (60.16 vs. 45.12%; P=0.033), multiple organ dysfunction syndrome (32.81 vs. 18.29%; P=0.021) and neurological deficits (30.47% vs. 17.07%, P=0.029) increased significantly. In conclusion, HF combined with COVID-19, treatment and prognosis are getting worse. Enhancing preparedness for future COVID-19 and other similar pandemics necessitates the comprehension of this to refine care provided to patients with HF (registration no. THH-IPR-20221101 on 01 November 2022).

Internal standard optimization advances sensitivity and robustness of ratiometric detection method.

We design a p-aminothiophenol (pATP) modified Au/ITO chip to determine nitrite ions in lake water by a ratiometric surface-enhanced Raman scattering (SERS) method based on nitrite ions triggering the transformation of pATP to p,p'-dimercaptoazobenzene (DMAB). Intriguingly, by using the SERS peak (at 1008 cm-1) from benzoic ring deforming as an internal standard instead of the traditional peak at 1080 cm-1, the detection sensitivity of the method was improved 10 times.

Enantiomer-Specific Colorimetric Tandem Assays for Salivary d-Alanine Associated with Gastric Cancer.

Salivary d-alanine (d-Ala) and d-proline (d-Pro) are of concern for their potential in the noninvasive diagnosis of gastric cancer (GC). Most reports have succeeded in determining the total concentration of d-Ala and d-Pro. However, for personalized diagnosis and better elucidation of the underlying specific correlation of d-Ala (or d-Pro) with GC, it is desirable to determine the specific concentration of d-Ala or d-Pro. Herein, we propose an enantiomer-specific tandem assay of d-Ala based on the colorimetric reaction between 2,4-dinitrophenylhydrazine and pyruvic acid generated from the deamination of d-Ala catalyzed by d-amino acid oxidase, which is easily distinguished from l-form amino acids, d-Pro, and many other species. A linear concentration range is established from 20 to 400 µmol/L with a limit of detection of 1.01 µmol/L. Real saliva sample tests reveal that the levels of d-Ala in GC cases are remarkably higher than those in healthy individuals, which offers a simple and low-cost strategy for GC diagnosis. Simultaneously, the total concentrations of d-Ala and d-Pro in saliva are determined. Hence, the concentration of d-Pro and the proportion of d-Ala could be calculated, which further provides more molecule- and individual-specific information. This research may offer a convenient method for noninvasive diagnosis of GC and pave a new route to explore the potentials of rare d-form amino acids in disease diagnosis and treatment.

Association between methotrexate-induced Stevens-Johnson syndrome/toxic epidermal necrolysis and furosemide: a real-world disproportionality analysis.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and life-threatening skin adverse reactions that are usually induced by drugs. This study aimed to assess the association between methotrexate and SJS/TEN when combined with furosemide. RESEARCH DESIGN AND METHODS: Data on suspicious, interactions (PS, SS, I) from the FDA Adverse Event Reporting System database for 2016-2021 were analyzed using the reporting odds ratio (ROR), information component (IC), proportional reporting ratio (PRR) and the Medications and Health Care Products Regulatory Agency (MHRA). RESULTS: We identified 28 case reports of TEN associated with the combination of furosemide and methotrexate and 10 reports of SJS associated with furosemide and methotrexate. The association of methotrexate with SJS/TEN was more significant in the entire data set when combined with furosemide than when methotrexate was not combined with furosemide. The association of methotrexate with SJS/TEN remained significant when furosemide was combined with methotrexate in a tumor-based disease context. After sensitivity analysis of the entire dataset as well as all antineoplastic drug datasets, consistent results were observed for TEN. CONCLUSIONS: Our study confirmed a significant association between methotrexate and SJS/TEN when combined with furosemide, with an increased risk of SJS/TEN.

Psoriasis and gut microbiota: A Mendelian randomization study.

In recent years, an increasing number of observational studies have revealed an association between gut microbiota composition and psoriasis patients. However, whether this association reflects a causal relationship remains unclear. This study aimed to identify the causal relationship between gut microbiota and psoriasis through relevant research. In order to determine whether gut microbiota and psoriasis are causally related, we conducted a Mendelian randomization analysis using summary statistics from genome-wide association studies (GWAS). As the exposure factor, we used summary statistics data from a GWAS study conducted by the MiBioGen Consortium, including 18,340 individuals with whole-genome gut microbiota composition, and data from the FinnGen GWAS study on psoriasis, including 9267 patients and 364,071 controls as the disease outcome. Two-sample Mendelian randomization analysis was subsequently performed with inverse variance weighted, MR-Egger and weighted median, while sensitivity analyses were conducted to address heterogeneity and horizontal pleiotropy. The IVW results confirmed the causal relationship between certain gut microbiota groups and psoriasis. Specifically, family Veillonellaceae (OR = 1.162, 95% CI: 1.038-1.301, p = 0.009), genus Candidatus Soleaferrea (OR = 1.123, 95% CI: 1.011-1.247, p = 0.030) and genus Eubacterium fissicatena group (OR = 0.831, 95% CI: 0.755-0.915, p = 0.00016) showed significant associations. Sensitivity analysis did not reveal any abnormalities in SNPs. Currently, we have found some causal relationship between the gut microbiota and psoriasis. However, the study needs further RCTs for further validation.

Optimal design of integrated visible light communication and positioning system with energy harvesting.

In this paper, an optimization scheme that can simultaneously transmit communication information, positioning the information and energy in a visible light communication and positioning (VLCP) system with energy harvesting is proposed. The time switching-power splitting (TS-PS) method is applied, where the power and time allocation factors are defined as optimization variables, so that the system can maximize the harvested energy under the constraints of the information rate and positioning error. The multi-verse optimization (MVO) algorithm is introduced to obtain the optimal power and time allocation. In addition, the performance of the integrated system using the TS-PS method is investigated and compared with that using other conventional methods. The results show that a maximized harvested energy solution using the TS-PS method can harvest the most energy. Moreover, the effects of main external environment conditions, namely, the room height and field of view (FoV) of a photo diode (PD) on the system performance are also analyzed. The increase of the room height and FoV of the PD reduces the harvested energy, but does not change the information rate and positioning accuracy in the optimized system adopted in this paper.

Genetically predicted 486 blood metabolites concerning risk of systemic lupus erythematosus: a Mendelian randomization study.

Metabolic abnormalities constitute a significant characteristic of systemic lupus erythematosus (SLE). We utilised a two-sample Mendelian randomisation (MR) study to evaluate the potential causal association between 486 blood metabolites and SLE. Exposure data at the metabolite level were extracted from 7824 European Genome-wide association studies (GWAS). Preliminary analysis utilised SLE GWAS data from FinnGen. The primary method for causal analysis relied on random inverse variance weighting (IVW). To ensure robustness, sensitivity analyses included the Cochran Q test, MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis. Steiger testing and linkage disequilibrium score regression were employed to validate the identified metabolites. This study identified 12 metabolites, comprising six known chemical structures: 1,5-anhydroglucitol(1,5-AG) [odds ratio (OR) = 0.100, 95% confidence interval (CI): 0.015-0.773, P = 0.027), gamma-glutamylthreonine (OR = 0.077, 95% CI: 0.010-0.574, P = 0.012), 5-dodecenoate(12:1n7) (OR = 0.205, 95% CI: 0.061-0.685, P = 0.010), linoleoylglycerophosphoethanolamine * (OR = 0.159, 95% CI: 0.027-0.933, P = 0.044), erythrose (OR = 88.331,95% CI:1.098-63.214, P = 0.040) and 1-, adrenate (22:4n6) (OR = 9.876, 95% CI: 1.753-55.639, P = 0.001)]. Additionally, we found associations between SLE and six unknown chemical structures: X-06351 (OR = 0.071, 95% CI: 0.006-0.817, P = 0.034), X-10810 (OR = 4.268 95% CI: 1.260-14.459, P = 0.020), X-11412 (OR = 5.418 95% CI: 1.068-27.487, P = 0.041), X-11905 (OR = 0.551, 95%CI: 0.304-0.997, P = 0.049), X-12038 (OR = 0.178 95%CI: 0.032-0.988, P = 0.045), X-12217 (OR = 0.174 95%CI: 0.044-0.680, P = 0.014). This study offers evidence supporting a causal relationship between SLE and 12 circulating metabolites, six of which have known chemical structures and six that remain unidentified. These findings introduce a new perspective for further exploration of SLE mechanisms.

Effects of Remote Ischemic Preconditioning on Delirium and Neurological Function in Patients Undergoing Cardiac Surgery: A Multicenter Randomized Controlled Trial.

BACKGROUND: Postoperative delirium (POD) and neurological dysfunction are very common following cardiac surgery and deteriorate the patient's prognosis and the outcome of surgical procedures. A clinically effective management strategy or drug is not yet available for POD. Additionally, it is unknown whether remote ischemic preconditioning (RIPC) has neuroprotective and anti-delirium benefits in patients who undergo cardiac surgery. METHODS: This study examined whether RIPC can improve POD and neurological function in cardiac surgery patients. We screened 510 consecutive adult patients aged 18 and older who underwent cardiac surgery between January 2018 and December 2022. Then, 448 of these patients were recruited in the trial as the intention to treat (ITT) group, who were then randomly assigned to receive either a control (n = 223) or RIPC treatment (n = 225). The primary outcome measures were hospitalization postoperative delirium, six-month modified Rankins scale (mRS), hospital cerebral infarction, 30-day overall mortality, neuron-specific enolase (NSE) and S-100b levels, related adverse effects, hospital costs, and hospital stay. RESULTS: A statistically significant variation was not observed between the two groups in terms of the baseline clinical data. In contrast to the control group, the POD in the RIPC group was considerably alleviated. RIPC treatment also decreased the levels of NSE and S-100b, which alleviated nerve injury. The adverse impacts of RIPC-induced objective indicators of tissue or neurovascular damage were similar in both groups, showing no significant variations between the two. The hospital stays and hospitalization costs also decreased significantly in the RIPC-treated patients. CONCLUSION: The study findings suggested that RIPC may benefit cardiac surgery patients by reducing POD, alleviating injury, and lowering hospital expenditures and length of stay. Cardiac surgery patients can be treated with RIPC, which is an effective and safe technique.

Surface-Enhanced Raman Scattering Enantioselective Detection of Gastric Cancer-Related d-Amino Acids in Saliva Based on Enzyme-Mediated Cascade Reaction.

The unusual d-amino acids (d-AAs), as the counter enantiomer of usual l-amino acids (l-AAs), have evoked increasing attention because of their potential relevance with diseases. Accordingly, it is essential to establish sensitive and selective detection methods for d-AAs without the interferences from l-AAs. The surface-enhanced Raman scattering (SERS) technique is efficacious for the detection of molecules but routinely ineffective in enantiomeric differentiation. d-Proline (d-Pro) and d-alanine (d-Ala) are regarded as biomarkers of gastric cancer. Herein, Raman-active boronate modified SERS chips are constructed to develop a d-amino acid oxidase (DAAO)-mediated cascade reaction-based SERS enantioselective assay for d-Pro and d-Ala. The principle is that DAAO selectively catalyzes the deamination of d-Pro and d-Ala, and the produced H2O2 oxidizes boronate to present a new SERS peak at 883 cm-1 for quantitative analysis in a ratiometric way. A linear range from 20 to 400 µmol/L and a limit of detection down to 14.8 µmol/L are reached. In addition, interferences from l-AAs and many other possible species coexisting in biofluids with the detection of d-Pro and d-Ala are ignorable. Enzyme-mediated cascade reaction-based SERS chips are further utilized for saliva sample analysis, and the total levels of d-Pro and d-Ala in salivary samples from gastric cancer patients are much higher than those of healthy persons. This work provides a solution for SERS enantioselective analysis and noninvasive screening chiral biomolecules for disease diagnosis.

The Perturbation Analysis of Nonconvex Low-Rank Matrix Robust Recovery.

In this article, we bring forward a completely perturbed nonconvex Schatten p -minimization to address a model of completely perturbed low-rank matrix recovery (LRMR). This article based on the restricted isometry property (RIP) and the Schatten- p null space property (NSP) generalizes the investigation to a complete perturbation model thinking over not only noise but also perturbation, and it gives the RIP condition and the Schatten- p NSP assumption that guarantee the recovery of low-rank matrix and the corresponding reconstruction error bounds. In particular, the analysis of the result reveals that in the case that p decreases 0 and for the complete perturbation and low-rank matrix, the condition is the optimal sufficient condition (Recht et al., 2010). In addition, we study the connection between RIP and Schatten- p NSP and discern that Schatten- p NSP can be inferred from the RIP. The numerical experiments are conducted to show better performance and provide outperformance of the nonconvex Schatten p -minimization method comparing with the convex nuclear norm minimization approach in the completely perturbed scenario.

Compounding warning letters to 503A facilities between 2017 and 2021.

BACKGROUND: The growing population demand and the epidemic lead of coronavirus disease 2019 have highlighted the critical importance of patient access to compounded formulations, including for special purposes such as pediatrics, geriatrics, and other uses. However, there are many potential risks, including quality issues and 503A facilities have not received valid prescriptions for individually-identified patients for a portion of the drug products they produce. OBJECTIVE: The aim is to analyze the (503A facilities) warning letters and identify the problem of compounding medicines not meeting the United States Pharmacopoeia specifications. METHODS: Content analysis and descriptive statistics methods were used to analyze the violations of compounding warning letters from 2017 to 2021. The content of warning letter violations was analyzed in terms of both the compounding environment and 503A facilities that did not received valid prescriptions for individually-identified patients for a portion of the drug products they produced. RESULTS: A total of 113 compounding warning letters (503A facilities, N = 112) from 2017 to 2021 were analyzed in this study. The percentage of 503A facilities involved in sterile compounding environmental issues was 79.46%, with facility design and environmental controls (73/89, 82.02%), cleaning and disinfecting the compounding area (59/89, 66.29%), and personnel cleansing and garbing (44/89, 49.44%) being the top 3 issues. Seventy-two (72/112, 64.29%) 503A facilities that did not received valid prescriptions for individually-identified patients for a portion of the drug products they produced. Fifty-one (51/72, 70.83%) of these warning letters were related to sterile environment issues, and 28 warning letters identified specific drugs that did not qualify for Section 503A exemptions. CONCLUSION: The warning letter of compounding drugs issued by Food and Drug Administration can be used as a learning tool for compounders. Compounders can learn from the experience and lessons, improve compounding operations and reduce mistakes.

FOXK2 regulates PFKFB3 in promoting glycolysis and tumorigenesis in multiple myeloma.

Forkhead box K2 (FOXK2) is a transcription factor involved in regulating the pathophysiological processes in many types of cancers. Functioning as either an oncogene or tumor suppressor, FOXK2 is involved in cell proliferation, metastasis, DNA damage, metabolism, and autophagy. However, the functions of FOXK2 in multiple myeloma (MM) are still unexplored. Here we show that FOXK2 silencing by small interfering RNA (siRNA) prevented the expression of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) via dephosphorylation of an AMP-activated protein kinase (AMPK). Consistently, suppression of FOXK2 inhibited glycolysis and cell proliferation in MM cells. Furthermore, the correlation between FOXK2 expression and disease progression in MM was evaluated using the TCGA (The Cancer Genome Atlas) database. Taken together, we identified a novel FOXK2-dependent signaling pathway involved in the regulation of PFKFB3 expression in response to glycolysis, which might serve as a potential therapeutic target in MM.

Metal ion-mediated modulation of morphology, physicochemical properties, and digestibility of type 3 resistant starch microparticle.

Short-chain glucan (SCG) derived from debranched amylopectin has emerged as a promising candidate for the production of resistant starch particle (RSP) due to its controllable self-assembly features. Here, we investigated the effect of metal cations with different valencies and concentrations on the morphology, physicochemical properties, and digestibility of RSP formed by the self-assembly of SCG. The effect of cations on the formation of RSP followed the valency in the following order: Na+, Ka+, Mg2+, Ca2+, Fe3+, and Al3+, of which 10 mM trivalent cations increased the particle size of RSP over 2 µm and considerably decreased the crystallinity by 49.5 % ~ 50.9 %, which were significantly different from that of mono- and divalent ones. Importantly, RSP formed with divalent cations switched the surface charge from -18.6 mV to 12.9 mV, which significantly increased the RS level, indicating that metal cations would be useful for regulating physicochemical properties and digestibility of RSP.

AcMADS32 positively regulates carotenoid biosynthesis in kiwifruit by activating AcBCH1/2 expression.

Fruits provide abundant carotenoid nutrients for humans, whereas the understanding of the transcriptional regulatory mechanisms of carotenoids in fruits is still limited. Here, we identified a transcription factor AcMADS32 in kiwifruit, which was highly expressed in the fruit, correlated with carotenoid content and localized in the nucleus. The silencing expression of AcMADS32 significantly reduced the content of ß-carotene and zeaxanthin and expression of ß-carotene hydroxylase gene AcBCH1/2 in kiwifruit, while transient overexpression increased the accumulation of zeaxanthin, suggesting that AcMADS32 was an activator involved in the transcriptional regulation of carotenoid in fruit. When AcMADS32 was further stably transformed into kiwifruit, the content of total carotenoid and components in the leaves of transgenic lines significantly increased, and the expression level of carotenogenic genes was up-regulated. Moreover, Y1H and dual luciferase reporter experiments confirmed that AcMADS32 directly bound the AcBCH1/2 promoter and activated its expression. Through Y2H assays, AcMADS32 can interact with other MADS transcription factor AcMADS30, AcMADS64 and AcMADS70. These findings will contribute to our understanding of the transcriptional regulation mechanisms underlying carotenoid biosynthesis in plants.

Reactive Hydrogel Patch for SERS Detection of Environmental Formaldehyde.

The tobacco epidemic is a public health threat that has taken a heavy toll of lives around the globe each year. As one of the poison species from smoking, formaldehyde (FA) affects both the smokers and nearby persons who are exposed to second-hand smoke. Therefore, on-site tracking of FA exposure could evaluate the public environmental safety and mitigate the potential hazards. Herein, we first prepare SiO2-shelled AuAg alloy nanoparticles (AuAg@SiO2) and then embed AuAg@SiO2 within agarose hydrogel to construct the three-dimensional (3D) surface-enhanced Raman scattering (SERS) substrate. A reagent of 3-methyl-2-benzothiazolinone hydrazine (MBTH) with reaction activity toward FA is loaded in the 3D substrate to obtain the selective SERS patch (designated as M-hydrogel patch). Based on a marker Raman peak at 1273 cm-1 from the reaction product of MBTH-FA, the M-hydrogel patch is used to realize SERS detection of FA in smoke. A good linear relationship from 5 × 10-4 to 5 mg/m3 and a limit of detection (LOD) of 2.92 × 10-5 mg/m3 could be reached. While for detection of FA in aqueous, a linear range of 1 × 10-7-1 × 10-3 mg/mL with an LOD of 1.46 × 10-8 mg/mL could be achieved. As the real application, the proposed M-hydrogel patch could be placed anywhere indoor to SERS evaluate the spatial distribution of FA in tobacco smoke, which is in connection with the second-hand smoke effect on children and adults. Such M-hydrogel patch-based SERS assay is exerted for on-field detection of FA in water and furniture panels by using a portable Raman system, showing satisfactory selectivity and reproducibility.

Pan-cancer analysis of super enhancer-induced PRR7-AS1 as a potential prognostic and immunological biomarker.

Introduction: Systematic pan-cancer analysis of the roles and regulatory mechanisms for PRR7-AS1 is currently not available. Methods: In the present study, a comprehensive bioinformatic approach was used to mine the underlying oncogenic effects of PRR7-AS1, including expression status, prognostic value and immune characteristics. Results: We discovered that PRR7-AS1 expression was remarkably upregulated in most cancer types and exhibited a negative correlation with the prognosis. Furthermore, PRR7-AS1 expression was inversely connected with the majority of tumor-infiltrating immune cells, immune scores and immune checkpoint gene expression in pancancer. There was also a significant correlation between PRR7-AS1 expression status and tumor mutational burden, microsatellite instability, and neoantigens in certain tumors. PRR7-AS1 had the best predictive power for immune checkpoint blockade efficacy compared to other well-recognized biomarkers. PRR7-AS1 overexpression could affect cytotoxic T cells-mediated antitumor responses. Functional enrichment analysis revealed that PRR7-AS1 might be involved in the metabolic pathways. Super enhancer activity might have participated in the regulation of PRR7-AS1 expression. And we constructed the competitive endogenous RNA networks for PRR7-AS1. Discussion: In general, PRR7-AS1 had the potential to be a diagnostic, prognostic and immune biomarker for pan cancer. PRR7-AS1 was correlated with an immunosuppressive microenvironment and was a new potential target for immunotherapy. Epigenetic factors were the driving forces for PRR7-AS1 overexpression in tumors.

Hexagon AgNCs/PVP Crystallization Induced Cathode Electrochemiluminescence Enhancement for miRNA221 Biosensing.

Aggredation-induced electrochemiluminescence (AIECL) promises an efficient strategy for synthesize highly luminescent emitter and co-reactant for ECL analysis, however, rational control of electrogenerated emission intensity is still challenging. The low electroconductivity and amorphous molecular configuration are intrinsic bottleneck. This work reveals the impact of polyvinyl pyrrolidone backbone regulated silver nanocrystallines (AgNCs/PVP) on the cathode AIECL properties in near infrared region, by employing the Box-Behnken designed response surface computation model to modulate crystal aggregates. Electron paramagnetic resonance spectroscopy discovered hydrogen radical (HO• ) dominant reductive-oxidative (R-O) ECL mechanism with AgNCs acting as the co-reaction accelerator in graphene oxide/persulfate system (GO/S2 O8 2- ). Both theoretical calculation and experimental measurement testified that the ECL of AgNCs in GO/S2 O8 2- dependent on the concentration of in situ electrochemical oxidized Ag+ . The high efficiency of crystallization-induced enhanced ECL (CIECL) originates from 1) the effective electron transfer of Ag+ accelerated HO• produce to notable promote radioactive transition, and 2) twisted intramolecular charge transfer from the electron-rich donor of PVP to electron-deficient receptor of Ag0 to restrict nonradioactive transition. The AgNCs/PVP with CIECL effect are applied to construct an ultrasensitive platform for miR-221 assay with a lower detection limit of 7.47 × 103  copies mL-1 than typical qPCR method.